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<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta name="robots" content="max-image-preview:large"> <meta name="access" content="No"> <meta name="360-site-verification" content="1268d79b5e96aecf3ff2a7dac04ad990" /> <title>Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells | Angiogenesis</title> <meta name="twitter:site" content="@SpringerLink"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image:alt" content="Content cover image"/> <meta name="twitter:title" content="Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells"/> <meta name="twitter:description" content="Angiogenesis - Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we..."/> <meta name="twitter:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig1_HTML.gif"/> <meta name="journal_id" content="10456"/> <meta name="dc.title" content="Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells"/> <meta name="dc.source" content="Angiogenesis 2011 15:1"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Springer"/> <meta name="dc.date" content="2011-12-20"/> <meta name="dc.type" content="OriginalPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2011 Springer Science+Business Media B.V."/> <meta name="dc.rights" content="2011 Springer Science+Business Media B.V."/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells."/> <meta name="prism.issn" content="1573-7209"/> <meta name="prism.publicationName" content="Angiogenesis"/> <meta name="prism.publicationDate" content="2011-12-20"/> <meta name="prism.volume" content="15"/> <meta name="prism.number" content="1"/> <meta name="prism.section" content="OriginalPaper"/> <meta name="prism.startingPage" content="47"/> <meta name="prism.endingPage" content="57"/> <meta name="prism.copyright" content="2011 Springer Science+Business Media B.V."/> <meta name="prism.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="prism.url" content="https://link.springer.com/article/10.1007/s10456-011-9242-0"/> <meta name="prism.doi" content="doi:10.1007/s10456-011-9242-0"/> <meta name="citation_pdf_url" content="https://link.springer.com/content/pdf/10.1007/s10456-011-9242-0.pdf"/> <meta name="citation_fulltext_html_url" content="https://link.springer.com/article/10.1007/s10456-011-9242-0"/> <meta name="citation_journal_title" content="Angiogenesis"/> <meta name="citation_journal_abbrev" content="Angiogenesis"/> <meta name="citation_publisher" content="Springer Netherlands"/> <meta name="citation_issn" content="1573-7209"/> <meta name="citation_title" content="Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells"/> <meta name="citation_volume" content="15"/> <meta name="citation_issue" content="1"/> <meta name="citation_publication_date" content="2012/03"/> <meta name="citation_online_date" content="2011/12/20"/> <meta name="citation_firstpage" content="47"/> <meta name="citation_lastpage" content="57"/> <meta name="citation_article_type" content="Original Paper"/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1007/s10456-011-9242-0"/> <meta name="DOI" content="10.1007/s10456-011-9242-0"/> <meta name="size" content="123924"/> <meta name="citation_doi" content="10.1007/s10456-011-9242-0"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1007/s10456-011-9242-0&api_key="/> <meta name="description" content="Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in"/> <meta name="dc.creator" content="Baldoli, Erika"/> <meta name="dc.creator" content="Maier, Jeanette A. M."/> <meta name="dc.subject" content="Cancer Research"/> <meta name="dc.subject" content="Biomedicine, general"/> <meta name="dc.subject" content="Cell Biology"/> <meta name="dc.subject" content="Cardiology"/> <meta name="dc.subject" content="Ophthalmology"/> <meta name="dc.subject" content="Oncology"/> <meta name="citation_reference" content="citation_journal_title=Nature; citation_title=Angiogenesis in life, disease and medicine; citation_author=P Carmeliet; citation_volume=438; citation_publication_date=2005; citation_pages=932-936; citation_doi=10.1038/nature04478; citation_id=CR1"/> <meta name="citation_reference" content="citation_journal_title=Cancer J; citation_title=Molecular predictors of response to antiangiogenesis therapies; citation_author=A Gerger, M Labonte, HJ Lenz; citation_volume=17; citation_publication_date=2011; citation_pages=134-141; citation_doi=10.1097/PPO.0b013e318212db3c; citation_id=CR2"/> <meta name="citation_reference" content="citation_journal_title=FASEB J; citation_title=Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes; citation_author=E Brakenhielm, R Cao, Y Cao; citation_volume=15; citation_publication_date=2001; citation_pages=1798-1800; citation_id=CR3"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biochem; citation_title=Flavonoids inhibit VEGF/bFGF-induced angiogenesis in vitro by inhibiting the matrix-degrading proteases; citation_author=MH Kim; citation_volume=89; citation_publication_date=2003; citation_pages=529-538; citation_doi=10.1002/jcb.10543; citation_id=CR4"/> <meta name="citation_reference" content="citation_journal_title=Nutr Rev; citation_title=A requirement for copper in angiogenesis; citation_author=ED Harris; citation_volume=62; citation_publication_date=2004; citation_pages=60-64; citation_doi=10.1111/j.1753-4887.2004.tb00025.x; citation_id=CR5"/> <meta name="citation_reference" content="citation_journal_title=Clin Sci; citation_title=Cell (patho)physiology of magnesium; citation_author=F Wolf, V Trapani; citation_volume=114; citation_publication_date=2008; citation_pages=27-35; citation_doi=10.1042/CS20070129; citation_id=CR6"/> <meta name="citation_reference" content="citation_journal_title=Biochim Biophys Acta; citation_title=Magnesium deficiency inhibits primary tumor growth but favors metastasis in mice; citation_author=A Nasulewicz, J Wietrzyk, FI Wolf, S Dzimira, JA Maier, Y Rayssiguier, A Mazur, A Opolski; citation_volume=1739; citation_publication_date=2004; citation_pages=26-32; citation_id=CR7"/> <meta name="citation_reference" content="citation_journal_title=Nutr Cancer; citation_title=Insights into the mechanisms involved in magnesium-dependent inhibition of primary tumor growth; citation_author=JA Maier, A Nasulewicz-Goldeman, M Simonacci, A Mazur, FI Wolf; citation_volume=59; citation_publication_date=2007; citation_pages=192-198; citation_doi=10.1080/01635580701420624; citation_id=CR8"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Magnesium deficiency causes loss of response to intermittent hypoxia in paraganglion cells; citation_author=S Torii, K Kobayashi, M Takahashi, K Katahira, K Goryo, N Matsushita, K Yasumoto, Y Fujii-Kuriyama, K Sogawa; citation_volume=284; citation_publication_date=2009; citation_pages=19077-19089; citation_doi=10.1074/jbc.M109.004424; citation_id=CR9"/> <meta name="citation_reference" content="citation_journal_title=Frontiers Biosci; citation_title=Magnesium and microvascular endothelial cells: a role in inflammation and angiogenesis; citation_author=D Bernardini, A Nasulewicz, A Mazur, JA Maier; citation_volume=10; citation_publication_date=2005; citation_pages=1177-1182; citation_doi=10.2741/1610; citation_id=CR10"/> <meta name="citation_reference" content="citation_journal_title=J Nutr; citation_title=Dietary magnesium intake in a national sample of US adults; citation_author=ES Ford, AH Mokdad; citation_volume=133; citation_publication_date=2003; citation_pages=2879-2882; citation_id=CR11"/> <meta name="citation_reference" content="citation_journal_title=Endocrinol Metab Clin North Am; citation_title=Disorders of magnesium metabolism; citation_author=JL Nadler, RK Rude; citation_volume=24; citation_publication_date=1995; citation_pages=623-641; citation_id=CR12"/> <meta name="citation_reference" content="citation_journal_title=Cancer Treatment Rev; citation_title=Magnesium and tumors: ally or foe?; citation_author=FI Wolf, AR Cittadini, JA Maier; citation_volume=35; citation_publication_date=2009; citation_pages=378-382; citation_doi=10.1016/j.ctrv.2009.01.003; citation_id=CR13"/> <meta name="citation_reference" content="citation_journal_title=Biochim Biophys Acta; citation_title=TRPM6 and TRPM7-Gatekeepers of human magnesium metabolism; citation_author=KP Schlingmann, S Waldegger, M Konrad, V Chubanov, T Gudermann; citation_volume=1772; citation_publication_date=2007; citation_pages=813-821; citation_id=CR14"/> <meta name="citation_reference" content="citation_journal_title=Nat Commun; citation_title=TRPM7 is essential for Mg homeostasis in mammals; citation_author=LV Ryazanova, LJ Rondon, S Zierler, Z Hu, J Galli, TP Yamaguchi, A Mazur, A Fleig, AG Ryazanov; citation_volume=1; citation_publication_date=2010; citation_pages=109; citation_doi=10.1038/ncomms1108; citation_id=CR15"/> <meta name="citation_reference" content="citation_journal_title=Int J Biochem Cell Biol; citation_title=HD-PTP inhibits endothelial migration through its interaction with Src; citation_author=M Mariotti, S Castiglioni, J Garcia-Manteiga, L Beguinot, JA Maier; citation_volume=41; citation_publication_date=2009; citation_pages=687-693; citation_doi=10.1016/j.biocel.2008.08.005; citation_id=CR16"/> <meta name="citation_reference" content="citation_journal_title=Lab Invest; citation_title=In vitro models of vasculogenesis and angiogenesis; citation_author=B Vailhé, D Vittet, J–J Feige; citation_volume=81; citation_publication_date=2001; citation_pages=439-452; citation_doi=10.1038/labinvest.3780252; citation_id=CR17"/> <meta name="citation_reference" content="citation_journal_title=Am J Physiol Cell Physiol; citation_title=Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor; citation_author=E Abed, R Moreau; citation_volume=297; citation_publication_date=2009; citation_pages=C360-C368; citation_doi=10.1152/ajpcell.00614.2008; citation_id=CR18"/> <meta name="citation_reference" content="citation_journal_title=Biochim Biophys Acta; citation_title=Magnesium deficiency promotes a proatherogenic phenotype in cultured human endothelial cells via activation of NFkB; citation_author=S Ferré, E Baldoli, M Leidi, JA Maier; citation_volume=1802; citation_publication_date=2010; citation_pages=952-958; citation_id=CR19"/> <meta name="citation_reference" content="citation_journal_title=Circ Res; citation_title=Influence of extracellular magnesium on capillary endothelial cell proliferation and migration; citation_author=S Banai, L Haggroth, SE Epstein, W Casscells; citation_volume=67; citation_publication_date=1990; citation_pages=645-650; citation_id=CR20"/> <meta name="citation_reference" content="citation_journal_title=Biochim Biophys Acta; citation_title=High concentrations of magnesium modulate vascular endothelial behaviour in vitro; citation_author=JA Maier, D Bernardini, Y Rayssiguier, A Mazur; citation_volume=1689; citation_publication_date=2004; citation_pages=6-12; citation_id=CR21"/> <meta name="citation_reference" content="citation_journal_title=Magnes Res; citation_title=Magnesium deficiency and endothelial dysfunction: is oxidative stress involved?; citation_author=FI Wolf, V Trapani, M Simonacci, S Ferré, JA Maier; citation_volume=21; citation_publication_date=2008; citation_pages=58-64; citation_id=CR22"/> <meta name="citation_reference" content="citation_journal_title=Am J Physiol Cell Physiol; citation_title=Evidence that TRPM7 is required for breast cancer cell proliferation; citation_author=A Guilbert, M Gautier, I Dhennin-Duthille, N Haren, H Sevestre; citation_volume=297; citation_issue=3; citation_publication_date=2009; citation_pages=C493-C502; citation_doi=10.1152/ajpcell.00624.2008; citation_id=CR23"/> <meta name="citation_reference" content="citation_journal_title=Cardiovasc Res; citation_title=Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway; citation_author=K Inoue, ZG Xiong; citation_volume=83; citation_issue=3; citation_publication_date=2009; citation_pages=547-557; citation_doi=10.1093/cvr/cvp153; citation_id=CR24"/> <meta name="citation_reference" content="citation_journal_title=Biochem Biophys Res Commun; citation_title=Vascular endothelial growth factor increases the intracellular magnesium; citation_author=BZ Hong, HS Kang, JN So, HN Kim, SA Park, SJ Kim, KR Kimm, YG Kwak; citation_volume=347; citation_publication_date=2006; citation_pages=496-501; citation_doi=10.1016/j.bbrc.2006.06.125; citation_id=CR25"/> <meta name="citation_reference" content="citation_journal_title=Mol and Cells; citation_title=Basic fibroblast growth factor increases intracellular magnesium concentration through the specific signaling pathways; citation_author=BZ Hong, SA Park, HN Kim, TZ Ma, HG Kim, HS Kang, YG Kwak; citation_volume=28; citation_publication_date=2009; citation_pages=13-17; citation_doi=10.1007/s10059-009-0103-2; citation_id=CR26"/> <meta name="citation_reference" content="citation_journal_title=Cell Signal; citation_title=Examination of the expanding pathways for the regulation of p21 expression and activity; citation_author=YS Jung, Y Qian, X Chen; citation_volume=22; citation_publication_date=2010; citation_pages=1003-1012; citation_doi=10.1016/j.cellsig.2010.01.013; citation_id=CR27"/> <meta name="citation_reference" content="citation_journal_title=Blood; citation_title=Humanized large-scale expanded endothelial colony—forming cells function in vitro and in vivo; citation_author=A Reinisch, NA Hofmann, K Obenauf, AC Kashofer, E Rohde, K Schallmoser, K Flicker, G Lanzer, W Linkesch, MR Speicher, D Strunk; citation_volume=11; citation_publication_date=2009; citation_pages=6716-6725; citation_doi=10.1182/blood-2008-09-181362; citation_id=CR28"/> <meta name="citation_reference" content="citation_journal_title=Biochim Biophys Acta; citation_title=Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis; citation_author=JA Maier, C Malpuech, W Zimowska, Y Rayssiguier, A Mazur; citation_volume=1689; citation_publication_date=2004; citation_pages=13-21; citation_id=CR29"/> <meta name="citation_reference" content="citation_journal_title=Arch Biochem Biophys; citation_title=Cellular magnesium homeostasis; citation_author=AM Romani; citation_volume=512; citation_publication_date=2011; citation_pages=1-23; citation_doi=10.1016/j.abb.2011.05.010; citation_id=CR30"/> <meta name="citation_reference" content="citation_journal_title=Proc Natl Acad Sci USA; citation_title=Endothelial cell diversity revealed by global expression profiling; citation_author=JT Chi, HY Chang, G Haraldsen, FL Jahnsen, OG Troyanskaya, DS Chang, Z Wang, SG Rockson, M Rijn, D Botstein, PO Brown; 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citation_author=E Abed, C Martineau, R Moreau; citation_volume=88; citation_issue=3; citation_publication_date=2011; citation_pages=246-253; citation_doi=10.1007/s00223-010-9455-z; citation_id=CR37"/> <meta name="citation_author" content="Baldoli, Erika"/> <meta name="citation_author_institution" content="Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Milano, Italy"/> <meta name="citation_author" content="Maier, Jeanette A. M."/> <meta name="citation_author_email" content="jeanette.maier@unimi.it"/> <meta name="citation_author_institution" content="Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Milano, Italy"/> <meta name="format-detection" content="telephone=no"/> <meta name="citation_cover_date" content="2012/03/01"/> <meta property="og:url" content="https://link.springer.com/article/10.1007/s10456-011-9242-0"/> <meta property="og:type" content="article"/> <meta property="og:site_name" content="SpringerLink"/> <meta property="og:title" content="Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells - Angiogenesis"/> <meta property="og:description" content="Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells."/> <meta property="og:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig1_HTML.gif"/> <meta name="format-detection" content="telephone=no"> <link rel="apple-touch-icon" sizes="180x180" href=/oscar-static/img/favicons/darwin/apple-touch-icon-92e819bf8a.png> <link rel="icon" type="image/png" sizes="192x192" href=/oscar-static/img/favicons/darwin/android-chrome-192x192-6f081ca7e5.png> <link rel="icon" type="image/png" sizes="32x32" href=/oscar-static/img/favicons/darwin/favicon-32x32-1435da3e82.png> <link rel="icon" type="image/png" sizes="16x16" href=/oscar-static/img/favicons/darwin/favicon-16x16-ed57f42bd2.png> <link rel="shortcut icon" data-test="shortcut-icon" href=/oscar-static/img/favicons/darwin/favicon-c6d59aafac.ico> <meta name="theme-color" content="#e6e6e6">   <link rel="stylesheet" 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Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells.","datePublished":"2011-12-20T00:00:00Z","dateModified":"2011-12-20T00:00:00Z","pageStart":"47","pageEnd":"57","sameAs":"https://doi.org/10.1007/s10456-011-9242-0","keywords":["Angiogenesis","TRPM7","Magnesium","Vascular endothelial cells","Cancer Research","Biomedicine","general","Cell Biology","Cardiology","Ophthalmology","Oncology"],"image":["https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig1_HTML.gif","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig2_HTML.gif","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig3_HTML.gif","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig4_HTML.gif","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig5_HTML.gif","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig6_HTML.gif","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig7_HTML.gif","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs10456-011-9242-0/MediaObjects/10456_2011_9242_Fig8_HTML.gif"],"isPartOf":{"name":"Angiogenesis","issn":["1573-7209","0969-6970"],"volumeNumber":"15","@type":["Periodical","PublicationVolume"]},"publisher":{"name":"Springer Netherlands","logo":{"url":"https://www.springernature.com/app-sn/public/images/logo-springernature.png","@type":"ImageObject"},"@type":"Organization"},"author":[{"name":"Erika Baldoli","affiliation":[{"name":"Università di Milano","address":{"name":"Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Milano, Italy","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Jeanette A. M. Maier","affiliation":[{"name":"Università di Milano","address":{"name":"Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Milano, Italy","@type":"PostalAddress"},"@type":"Organization"}],"email":"jeanette.maier@unimi.it","@type":"Person"}],"isAccessibleForFree":false,"hasPart":{"isAccessibleForFree":false,"cssSelector":".main-content","@type":"WebPageElement"},"@type":"ScholarlyArticle"},"@context":"https://schema.org","@type":"WebPage"}</script> </head> <body class="" >  <noscript> <iframe src="https://www.googletagmanager.com/ns.html?id=GTM-MRVXSHQ" height="0" width="0" style="display:none;visibility:hidden"></iframe> </noscript>   <noscript data-test="gtm-body"> <iframe src="https://www.googletagmanager.com/ns.html?id=GTM-MRVXSHQ" height="0" width="0" style="display:none;visibility:hidden"></iframe> </noscript>  <div class="u-visually-hidden" aria-hidden="true" data-test="darwin-icons"> <?xml version="1.0" encoding="UTF-8"?><!DOCTYPE svg PUBLIC "-//W3C//DTD SVG 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alt=""> </picture> <span class="app-article-masthead__journal-title">Angiogenesis</span> </a> <a href="https://link.springer.com/journal/10456/aims-and-scope" class="app-article-masthead__submission-link" data-track="click_aims_and_scope" data-track-action="aims and scope" data-track-context="article page" data-track-label="link"> Aims and scope <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-arrow-right-medium"></use></svg> </a> <a href="https://submission.nature.com/new-submission/10456/3" class="app-article-masthead__submission-link" data-track="click_submit_manuscript" data-track-context="article masthead on springerlink article page" data-track-action="submit manuscript" data-track-label="link"> Submit manuscript <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-arrow-right-medium"></use></svg> </a> </div> </div> </div> </section> <div class="c-article-main u-container u-mt-24 u-mb-32 l-with-sidebar" id="main-content" data-component="article-container"> <main class="u-serif js-main-column" data-track-component="article body"> <div class="c-article-header"> <header> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Erika-Baldoli-Aff1" data-author-popup="auth-Erika-Baldoli-Aff1" data-author-search="Baldoli, Erika">Erika Baldoli</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup> & </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Jeanette_A__M_-Maier-Aff1" data-author-popup="auth-Jeanette_A__M_-Maier-Aff1" data-author-search="Maier, Jeanette A. M." data-corresp-id="c1">Jeanette A. M. Maier<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a></sup> </li></ul> <div data-test="article-metrics"> <ul class="app-article-metrics-bar u-list-reset"> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-accesses-medium"></use> </svg>1073 <span class="app-article-metrics-bar__label">Accesses</span></p> </li> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-citations-medium"></use> </svg>70 <span class="app-article-metrics-bar__label">Citations</span></p> </li> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-altmetric-medium"></use> </svg>5 <span class="app-article-metrics-bar__label">Altmetric</span></p> </li> <li class="app-article-metrics-bar__item app-article-metrics-bar__item--metrics"> <p class="app-article-metrics-bar__details"><a href="/article/10.1007/s10456-011-9242-0/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Explore all metrics <svg class="u-icon app-article-metrics-bar__arrow-icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-arrow-right-medium"></use> </svg></a></p> </li> </ul> </div> <div class="u-mt-32"> </div> </header> </div> <div data-article-body="true" data-track-component="article body" class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. 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u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>HMEC:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Human microvascular endothelial cells</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>HUVEC:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Human endothelial cells of the umbilical vein</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>Mg:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Magnesium</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>MMP:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Matrix metalloproteases</p> </dd><dt class="c-abbreviation_list__term u-text-bold u-float-left u-pr-16" style="min-width:50px;"><dfn>FBS:</dfn></dt><dd class="c-abbreviation_list__description u-mb-24"> <p>Fetal bovine serum</p> </dd></dl></div></div></section><div id="MagazineFulltextArticleBodySuffix"><section aria-labelledby="Bib1" data-title="References"><div class="c-article-section" id="Bib1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Bib1">References</h2><div class="c-article-section__content" id="Bib1-content"><div data-container-section="references"><ol class="c-article-references" data-track-component="outbound reference" data-track-context="references section"><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="1."><p class="c-article-references__text" id="ref-CR1">Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/nature04478" data-track-item_id="10.1038/nature04478" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fnature04478" aria-label="Article reference 1" data-doi="10.1038/nature04478">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16355210" aria-label="PubMed reference 1">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2MXhtlSksrjF" aria-label="CAS reference 1">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 1" href="http://scholar.google.com/scholar_lookup?&title=Angiogenesis%20in%20life%2C%20disease%20and%20medicine&journal=Nature&doi=10.1038%2Fnature04478&volume=438&pages=932-936&publication_year=2005&author=Carmeliet%2CP"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="2."><p class="c-article-references__text" id="ref-CR2">Gerger A, Labonte M, Lenz HJ (2011) Molecular predictors of response to antiangiogenesis therapies. Cancer J 17:134–141</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1097/PPO.0b013e318212db3c" data-track-item_id="10.1097/PPO.0b013e318212db3c" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1097%2FPPO.0b013e318212db3c" aria-label="Article reference 2" data-doi="10.1097/PPO.0b013e318212db3c">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21427557" aria-label="PubMed reference 2">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXmtVKnsLc%3D" aria-label="CAS reference 2">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 2" href="http://scholar.google.com/scholar_lookup?&title=Molecular%20predictors%20of%20response%20to%20antiangiogenesis%20therapies&journal=Cancer%20J&doi=10.1097%2FPPO.0b013e318212db3c&volume=17&pages=134-141&publication_year=2011&author=Gerger%2CA&author=Labonte%2CM&author=Lenz%2CHJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="3."><p class="c-article-references__text" id="ref-CR3">Brakenhielm E, Cao R, Cao Y (2001) Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J 15:1798–1800</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11481234" aria-label="PubMed reference 3">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3MXmsFejsrY%3D" aria-label="CAS reference 3">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 3" href="http://scholar.google.com/scholar_lookup?&title=Suppression%20of%20angiogenesis%2C%20tumor%20growth%2C%20and%20wound%20healing%20by%20resveratrol%2C%20a%20natural%20compound%20in%20red%20wine%20and%20grapes&journal=FASEB%20J&volume=15&pages=1798-1800&publication_year=2001&author=Brakenhielm%2CE&author=Cao%2CR&author=Cao%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="4."><p class="c-article-references__text" id="ref-CR4">Kim MH (2003) Flavonoids inhibit VEGF/bFGF-induced angiogenesis in vitro by inhibiting the matrix-degrading proteases. J Cell Biochem 89:529–538</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1002/jcb.10543" data-track-item_id="10.1002/jcb.10543" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1002%2Fjcb.10543" aria-label="Article reference 4" data-doi="10.1002/jcb.10543">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12761886" aria-label="PubMed reference 4">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXksVKktbs%3D" aria-label="CAS reference 4">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 4" href="http://scholar.google.com/scholar_lookup?&title=Flavonoids%20inhibit%20VEGF%2FbFGF-induced%20angiogenesis%20in%20vitro%20by%20inhibiting%20the%20matrix-degrading%20proteases&journal=J%20Cell%20Biochem&doi=10.1002%2Fjcb.10543&volume=89&pages=529-538&publication_year=2003&author=Kim%2CMH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="5."><p class="c-article-references__text" id="ref-CR5">Harris ED (2004) A requirement for copper in angiogenesis. Nutr Rev 62:60–64</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1111/j.1753-4887.2004.tb00025.x" data-track-item_id="10.1111/j.1753-4887.2004.tb00025.x" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1111%2Fj.1753-4887.2004.tb00025.x" aria-label="Article reference 5" data-doi="10.1111/j.1753-4887.2004.tb00025.x">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15080367" aria-label="PubMed reference 5">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 5" href="http://scholar.google.com/scholar_lookup?&title=A%20requirement%20for%20copper%20in%20angiogenesis&journal=Nutr%20Rev&doi=10.1111%2Fj.1753-4887.2004.tb00025.x&volume=62&pages=60-64&publication_year=2004&author=Harris%2CED"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="6."><p class="c-article-references__text" id="ref-CR6">Wolf F, Trapani V (2008) Cell (patho)physiology of magnesium. Clin Sci 114:27–35</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1042/CS20070129" data-track-item_id="10.1042/CS20070129" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1042%2FCS20070129" aria-label="Article reference 6" data-doi="10.1042/CS20070129">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18047467" aria-label="PubMed reference 6">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXhtlKru7bJ" aria-label="CAS reference 6">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 6" href="http://scholar.google.com/scholar_lookup?&title=Cell%20%28patho%29physiology%20of%20magnesium&journal=Clin%20Sci&doi=10.1042%2FCS20070129&volume=114&pages=27-35&publication_year=2008&author=Wolf%2CF&author=Trapani%2CV"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="7."><p class="c-article-references__text" id="ref-CR7">Nasulewicz A, Wietrzyk J, Wolf FI, Dzimira S, Maier JA, Rayssiguier Y, Mazur A, Opolski A (2004) Magnesium deficiency inhibits primary tumor growth but favors metastasis in mice. Biochim Biophys Acta 1739:26–32</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15607114" aria-label="PubMed reference 7">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXhtVOitbfJ" aria-label="CAS reference 7">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 7" href="http://scholar.google.com/scholar_lookup?&title=Magnesium%20deficiency%20inhibits%20primary%20tumor%20growth%20but%20favors%20metastasis%20in%20mice&journal=Biochim%20Biophys%20Acta&volume=1739&pages=26-32&publication_year=2004&author=Nasulewicz%2CA&author=Wietrzyk%2CJ&author=Wolf%2CFI&author=Dzimira%2CS&author=Maier%2CJA&author=Rayssiguier%2CY&author=Mazur%2CA&author=Opolski%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="8."><p class="c-article-references__text" id="ref-CR8">Maier JA, Nasulewicz-Goldeman A, Simonacci M, Mazur A, Wolf FI (2007) Insights into the mechanisms involved in magnesium-dependent inhibition of primary tumor growth. Nutr Cancer 59:192–198</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1080/01635580701420624" data-track-item_id="10.1080/01635580701420624" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1080%2F01635580701420624" aria-label="Article reference 8" data-doi="10.1080/01635580701420624">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18001214" aria-label="PubMed reference 8">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXhsVGgtrzL" aria-label="CAS reference 8">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 8" href="http://scholar.google.com/scholar_lookup?&title=Insights%20into%20the%20mechanisms%20involved%20in%20magnesium-dependent%20inhibition%20of%20primary%20tumor%20growth&journal=Nutr%20Cancer&doi=10.1080%2F01635580701420624&volume=59&pages=192-198&publication_year=2007&author=Maier%2CJA&author=Nasulewicz-Goldeman%2CA&author=Simonacci%2CM&author=Mazur%2CA&author=Wolf%2CFI"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="9."><p class="c-article-references__text" id="ref-CR9">Torii S, Kobayashi K, Takahashi M, Katahira K, Goryo K, Matsushita N, Yasumoto K, Fujii-Kuriyama Y, Sogawa K (2009) Magnesium deficiency causes loss of response to intermittent hypoxia in paraganglion cells. J Biol Chem 284:19077–19089</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1074/jbc.M109.004424" data-track-item_id="10.1074/jbc.M109.004424" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1074%2Fjbc.M109.004424" aria-label="Article reference 9" data-doi="10.1074/jbc.M109.004424">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19433582" aria-label="PubMed reference 9">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXotVKnt7g%3D" aria-label="CAS reference 9">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 9" href="http://scholar.google.com/scholar_lookup?&title=Magnesium%20deficiency%20causes%20loss%20of%20response%20to%20intermittent%20hypoxia%20in%20paraganglion%20cells&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M109.004424&volume=284&pages=19077-19089&publication_year=2009&author=Torii%2CS&author=Kobayashi%2CK&author=Takahashi%2CM&author=Katahira%2CK&author=Goryo%2CK&author=Matsushita%2CN&author=Yasumoto%2CK&author=Fujii-Kuriyama%2CY&author=Sogawa%2CK"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="10."><p class="c-article-references__text" id="ref-CR10">Bernardini D, Nasulewicz A, Mazur A, Maier JA (2005) Magnesium and microvascular endothelial cells: a role in inflammation and angiogenesis. Frontiers Biosci 10:1177–1182</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.2741/1610" data-track-item_id="10.2741/1610" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.2741%2F1610" aria-label="Article reference 10" data-doi="10.2741/1610">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2MXisVektLk%3D" aria-label="CAS reference 10">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 10" href="http://scholar.google.com/scholar_lookup?&title=Magnesium%20and%20microvascular%20endothelial%20cells%3A%20a%20role%20in%20inflammation%20and%20angiogenesis&journal=Frontiers%20Biosci&doi=10.2741%2F1610&volume=10&pages=1177-1182&publication_year=2005&author=Bernardini%2CD&author=Nasulewicz%2CA&author=Mazur%2CA&author=Maier%2CJA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="11."><p class="c-article-references__text" id="ref-CR11">Ford ES, Mokdad AH (2003) Dietary magnesium intake in a national sample of US adults. J Nutr 133:2879–2882</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12949381" aria-label="PubMed reference 11">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXntlaks7o%3D" aria-label="CAS reference 11">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 11" href="http://scholar.google.com/scholar_lookup?&title=Dietary%20magnesium%20intake%20in%20a%20national%20sample%20of%20US%20adults&journal=J%20Nutr&volume=133&pages=2879-2882&publication_year=2003&author=Ford%2CES&author=Mokdad%2CAH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="12."><p class="c-article-references__text" id="ref-CR12">Nadler JL, Rude RK (1995) Disorders of magnesium metabolism. Endocrinol Metab Clin North Am 24:623–641</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8575413" aria-label="PubMed reference 12">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:STN:280:DyaK287gs1Knsg%3D%3D" aria-label="CAS reference 12">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 12" href="http://scholar.google.com/scholar_lookup?&title=Disorders%20of%20magnesium%20metabolism&journal=Endocrinol%20Metab%20Clin%20North%20Am&volume=24&pages=623-641&publication_year=1995&author=Nadler%2CJL&author=Rude%2CRK"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="13."><p class="c-article-references__text" id="ref-CR13">Wolf FI, Cittadini AR, Maier JA (2009) Magnesium and tumors: ally or foe? Cancer Treatment Rev 35:378–382</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.ctrv.2009.01.003" data-track-item_id="10.1016/j.ctrv.2009.01.003" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.ctrv.2009.01.003" aria-label="Article reference 13" data-doi="10.1016/j.ctrv.2009.01.003">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXmtlOqtrs%3D" aria-label="CAS reference 13">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 13" href="http://scholar.google.com/scholar_lookup?&title=Magnesium%20and%20tumors%3A%20ally%20or%20foe%3F&journal=Cancer%20Treatment%20Rev&doi=10.1016%2Fj.ctrv.2009.01.003&volume=35&pages=378-382&publication_year=2009&author=Wolf%2CFI&author=Cittadini%2CAR&author=Maier%2CJA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="14."><p class="c-article-references__text" id="ref-CR14">Schlingmann KP, Waldegger S, Konrad M, Chubanov V, Gudermann T (2007) TRPM6 and TRPM7-Gatekeepers of human magnesium metabolism. Biochim Biophys Acta 1772:813–821</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17481860" aria-label="PubMed reference 14">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXosFOjt7c%3D" aria-label="CAS reference 14">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 14" href="http://scholar.google.com/scholar_lookup?&title=TRPM6%20and%20TRPM7-Gatekeepers%20of%20human%20magnesium%20metabolism&journal=Biochim%20Biophys%20Acta&volume=1772&pages=813-821&publication_year=2007&author=Schlingmann%2CKP&author=Waldegger%2CS&author=Konrad%2CM&author=Chubanov%2CV&author=Gudermann%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="15."><p class="c-article-references__text" id="ref-CR15">Ryazanova LV, Rondon LJ, Zierler S, Hu Z, Galli J, Yamaguchi TP, Mazur A, Fleig A, Ryazanov AG (2010) TRPM7 is essential for Mg homeostasis in mammals. Nat Commun 1:109</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/ncomms1108" data-track-item_id="10.1038/ncomms1108" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fncomms1108" aria-label="Article reference 15" data-doi="10.1038/ncomms1108">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21045827" aria-label="PubMed reference 15">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 15" href="http://scholar.google.com/scholar_lookup?&title=TRPM7%20is%20essential%20for%20Mg%20homeostasis%20in%20mammals&journal=Nat%20Commun&doi=10.1038%2Fncomms1108&volume=1&publication_year=2010&author=Ryazanova%2CLV&author=Rondon%2CLJ&author=Zierler%2CS&author=Hu%2CZ&author=Galli%2CJ&author=Yamaguchi%2CTP&author=Mazur%2CA&author=Fleig%2CA&author=Ryazanov%2CAG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="16."><p class="c-article-references__text" id="ref-CR16">Mariotti M, Castiglioni S, Garcia-Manteiga J, Beguinot L, Maier JA (2009) HD-PTP inhibits endothelial migration through its interaction with Src. Int J Biochem Cell Biol 41:687–693</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.biocel.2008.08.005" data-track-item_id="10.1016/j.biocel.2008.08.005" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.biocel.2008.08.005" aria-label="Article reference 16" data-doi="10.1016/j.biocel.2008.08.005">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18762272" aria-label="PubMed reference 16">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXns1yisQ%3D%3D" aria-label="CAS reference 16">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 16" href="http://scholar.google.com/scholar_lookup?&title=HD-PTP%20inhibits%20endothelial%20migration%20through%20its%20interaction%20with%20Src&journal=Int%20J%20Biochem%20Cell%20Biol&doi=10.1016%2Fj.biocel.2008.08.005&volume=41&pages=687-693&publication_year=2009&author=Mariotti%2CM&author=Castiglioni%2CS&author=Garcia-Manteiga%2CJ&author=Beguinot%2CL&author=Maier%2CJA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="17."><p class="c-article-references__text" id="ref-CR17">Vailhé B, Vittet D, Feige J–J (2001) In vitro models of vasculogenesis and angiogenesis. Lab Invest 81:439–452</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/labinvest.3780252" data-track-item_id="10.1038/labinvest.3780252" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Flabinvest.3780252" aria-label="Article reference 17" data-doi="10.1038/labinvest.3780252">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11304563" aria-label="PubMed reference 17">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 17" href="http://scholar.google.com/scholar_lookup?&title=In%20vitro%20models%20of%20vasculogenesis%20and%20angiogenesis&journal=Lab%20Invest&doi=10.1038%2Flabinvest.3780252&volume=81&pages=439-452&publication_year=2001&author=Vailh%C3%A9%2CB&author=Vittet%2CD&author=Feige%2CJ%E2%80%93J"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="18."><p class="c-article-references__text" id="ref-CR18">Abed E, Moreau R (2009) Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor. Am J Physiol Cell Physiol 297:C360–C368</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1152/ajpcell.00614.2008" data-track-item_id="10.1152/ajpcell.00614.2008" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1152%2Fajpcell.00614.2008" aria-label="Article reference 18" data-doi="10.1152/ajpcell.00614.2008">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19474290" aria-label="PubMed reference 18">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXhtVahsbvF" aria-label="CAS reference 18">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 18" href="http://scholar.google.com/scholar_lookup?&title=Importance%20of%20melastatin-like%20transient%20receptor%20potential%207%20and%20magnesium%20in%20the%20stimulation%20of%20osteoblast%20proliferation%20and%20migration%20by%20platelet-derived%20growth%20factor&journal=Am%20J%20Physiol%20Cell%20Physiol&doi=10.1152%2Fajpcell.00614.2008&volume=297&pages=C360-C368&publication_year=2009&author=Abed%2CE&author=Moreau%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="19."><p class="c-article-references__text" id="ref-CR19">Ferré S, Baldoli E, Leidi M, Maier JA (2010) Magnesium deficiency promotes a proatherogenic phenotype in cultured human endothelial cells via activation of NFkB. Biochim Biophys Acta 1802:952–958</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20600865" aria-label="PubMed reference 19">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 19" href="http://scholar.google.com/scholar_lookup?&title=Magnesium%20deficiency%20promotes%20a%20proatherogenic%20phenotype%20in%20cultured%20human%20endothelial%20cells%20via%20activation%20of%20NFkB&journal=Biochim%20Biophys%20Acta&volume=1802&pages=952-958&publication_year=2010&author=Ferr%C3%A9%2CS&author=Baldoli%2CE&author=Leidi%2CM&author=Maier%2CJA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="20."><p class="c-article-references__text" id="ref-CR20">Banai S, Haggroth L, Epstein SE, Casscells W (1990) Influence of extracellular magnesium on capillary endothelial cell proliferation and migration. Circ Res 67:645–650</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=1697793" aria-label="PubMed reference 20">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK3MXhtF2mt74%3D" aria-label="CAS reference 20">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 20" href="http://scholar.google.com/scholar_lookup?&title=Influence%20of%20extracellular%20magnesium%20on%20capillary%20endothelial%20cell%20proliferation%20and%20migration&journal=Circ%20Res&volume=67&pages=645-650&publication_year=1990&author=Banai%2CS&author=Haggroth%2CL&author=Epstein%2CSE&author=Casscells%2CW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="21."><p class="c-article-references__text" id="ref-CR21">Maier JA, Bernardini D, Rayssiguier Y, Mazur A (2004) High concentrations of magnesium modulate vascular endothelial behaviour in vitro. Biochim Biophys Acta 1689:6–12</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15158908" aria-label="PubMed reference 21">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXktF2rsbg%3D" aria-label="CAS reference 21">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 21" href="http://scholar.google.com/scholar_lookup?&title=High%20concentrations%20of%20magnesium%20modulate%20vascular%20endothelial%20behaviour%20in%20vitro&journal=Biochim%20Biophys%20Acta&volume=1689&pages=6-12&publication_year=2004&author=Maier%2CJA&author=Bernardini%2CD&author=Rayssiguier%2CY&author=Mazur%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="22."><p class="c-article-references__text" id="ref-CR22">Wolf FI, Trapani V, Simonacci M, Ferré S, Maier JA (2008) Magnesium deficiency and endothelial dysfunction: is oxidative stress involved? Magnes Res 21:58–64</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18557135" aria-label="PubMed reference 22">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXlt1Wku7s%3D" aria-label="CAS reference 22">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 22" href="http://scholar.google.com/scholar_lookup?&title=Magnesium%20deficiency%20and%20endothelial%20dysfunction%3A%20is%20oxidative%20stress%20involved%3F&journal=Magnes%20Res&volume=21&pages=58-64&publication_year=2008&author=Wolf%2CFI&author=Trapani%2CV&author=Simonacci%2CM&author=Ferr%C3%A9%2CS&author=Maier%2CJA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="23."><p class="c-article-references__text" id="ref-CR23">Guilbert A, Gautier M, Dhennin-Duthille I, Haren N, Sevestre H et al (2009) Evidence that TRPM7 is required for breast cancer cell proliferation. Am J Physiol Cell Physiol 297(3):C493–C502</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1152/ajpcell.00624.2008" data-track-item_id="10.1152/ajpcell.00624.2008" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1152%2Fajpcell.00624.2008" aria-label="Article reference 23" data-doi="10.1152/ajpcell.00624.2008">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19515901" aria-label="PubMed reference 23">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXht1yktbrP" aria-label="CAS reference 23">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 23" href="http://scholar.google.com/scholar_lookup?&title=Evidence%20that%20TRPM7%20is%20required%20for%20breast%20cancer%20cell%20proliferation&journal=Am%20J%20Physiol%20Cell%20Physiol&doi=10.1152%2Fajpcell.00624.2008&volume=297&issue=3&pages=C493-C502&publication_year=2009&author=Guilbert%2CA&author=Gautier%2CM&author=Dhennin-Duthille%2CI&author=Haren%2CN&author=Sevestre%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="24."><p class="c-article-references__text" id="ref-CR24">Inoue K, Xiong ZG (2009) Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway. Cardiovasc Res 83(3):547–557</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1093/cvr/cvp153" data-track-item_id="10.1093/cvr/cvp153" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1093%2Fcvr%2Fcvp153" aria-label="Article reference 24" data-doi="10.1093/cvr/cvp153">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19454490" aria-label="PubMed reference 24">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXovVeqsrg%3D" aria-label="CAS reference 24">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 24" href="http://scholar.google.com/scholar_lookup?&title=Silencing%20TRPM7%20promotes%20growth%2Fproliferation%20and%20nitric%20oxide%20production%20of%20vascular%20endothelial%20cells%20via%20the%20ERK%20pathway&journal=Cardiovasc%20Res&doi=10.1093%2Fcvr%2Fcvp153&volume=83&issue=3&pages=547-557&publication_year=2009&author=Inoue%2CK&author=Xiong%2CZG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="25."><p class="c-article-references__text" id="ref-CR25">Hong BZ, Kang HS, So JN, Kim HN, Park SA, Kim SJ, Kimm KR, Kwak YG (2006) Vascular endothelial growth factor increases the intracellular magnesium. Biochem Biophys Res Commun 347:496–501</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.bbrc.2006.06.125" data-track-item_id="10.1016/j.bbrc.2006.06.125" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.bbrc.2006.06.125" aria-label="Article reference 25" data-doi="10.1016/j.bbrc.2006.06.125">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16828056" aria-label="PubMed reference 25">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28XntFWktLc%3D" aria-label="CAS reference 25">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 25" href="http://scholar.google.com/scholar_lookup?&title=Vascular%20endothelial%20growth%20factor%20increases%20the%20intracellular%20magnesium&journal=Biochem%20Biophys%20Res%20Commun&doi=10.1016%2Fj.bbrc.2006.06.125&volume=347&pages=496-501&publication_year=2006&author=Hong%2CBZ&author=Kang%2CHS&author=So%2CJN&author=Kim%2CHN&author=Park%2CSA&author=Kim%2CSJ&author=Kimm%2CKR&author=Kwak%2CYG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="26."><p class="c-article-references__text" id="ref-CR26">Hong BZ, Park SA, Kim HN, Ma TZ, Kim HG, Kang HS, Kwak YG (2009) Basic fibroblast growth factor increases intracellular magnesium concentration through the specific signaling pathways. Mol and Cells 28:13–17</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="noopener" data-track-label="10.1007/s10059-009-0103-2" data-track-item_id="10.1007/s10059-009-0103-2" data-track-value="article reference" data-track-action="article reference" href="https://link.springer.com/doi/10.1007/s10059-009-0103-2" aria-label="Article reference 26" data-doi="10.1007/s10059-009-0103-2">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXhtVCgu7vF" aria-label="CAS reference 26">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 26" href="http://scholar.google.com/scholar_lookup?&title=Basic%20fibroblast%20growth%20factor%20increases%20intracellular%20magnesium%20concentration%20through%20the%20specific%20signaling%20pathways&journal=Mol%20and%20Cells&doi=10.1007%2Fs10059-009-0103-2&volume=28&pages=13-17&publication_year=2009&author=Hong%2CBZ&author=Park%2CSA&author=Kim%2CHN&author=Ma%2CTZ&author=Kim%2CHG&author=Kang%2CHS&author=Kwak%2CYG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="27."><p class="c-article-references__text" id="ref-CR27">Jung YS, Qian Y, Chen X (2010) Examination of the expanding pathways for the regulation of p21 expression and activity. Cell Signal 22:1003–1012</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.cellsig.2010.01.013" data-track-item_id="10.1016/j.cellsig.2010.01.013" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.cellsig.2010.01.013" aria-label="Article reference 27" data-doi="10.1016/j.cellsig.2010.01.013">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20100570" aria-label="PubMed reference 27">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXlt1Clurs%3D" aria-label="CAS reference 27">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 27" href="http://scholar.google.com/scholar_lookup?&title=Examination%20of%20the%20expanding%20pathways%20for%20the%20regulation%20of%20p21%20expression%20and%20activity&journal=Cell%20Signal&doi=10.1016%2Fj.cellsig.2010.01.013&volume=22&pages=1003-1012&publication_year=2010&author=Jung%2CYS&author=Qian%2CY&author=Chen%2CX"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="28."><p class="c-article-references__text" id="ref-CR28">Reinisch A, Hofmann NA, Obenauf K, Kashofer AC, Rohde E, Schallmoser K, Flicker K, Lanzer G, Linkesch W, Speicher MR, Strunk D (2009) Humanized large-scale expanded endothelial colony—forming cells function in vitro and in vivo. Blood 11:6716–6725</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1182/blood-2008-09-181362" data-track-item_id="10.1182/blood-2008-09-181362" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1182%2Fblood-2008-09-181362" aria-label="Article reference 28" data-doi="10.1182/blood-2008-09-181362">Article</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 28" href="http://scholar.google.com/scholar_lookup?&title=Humanized%20large-scale%20expanded%20endothelial%20colony%E2%80%94forming%20cells%20function%20in%20vitro%20and%20in%20vivo&journal=Blood&doi=10.1182%2Fblood-2008-09-181362&volume=11&pages=6716-6725&publication_year=2009&author=Reinisch%2CA&author=Hofmann%2CNA&author=Obenauf%2CK&author=Kashofer%2CAC&author=Rohde%2CE&author=Schallmoser%2CK&author=Flicker%2CK&author=Lanzer%2CG&author=Linkesch%2CW&author=Speicher%2CMR&author=Strunk%2CD"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="29."><p class="c-article-references__text" id="ref-CR29">Maier JA, Malpuech C, Zimowska W, Rayssiguier Y, Mazur A (2004) Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis. Biochim Biophys Acta 1689:13–21</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15158909" aria-label="PubMed reference 29">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXktF2rsbk%3D" aria-label="CAS reference 29">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 29" href="http://scholar.google.com/scholar_lookup?&title=Low%20magnesium%20promotes%20endothelial%20cell%20dysfunction%3A%20implications%20for%20atherosclerosis%2C%20inflammation%20and%20thrombosis&journal=Biochim%20Biophys%20Acta&volume=1689&pages=13-21&publication_year=2004&author=Maier%2CJA&author=Malpuech%2CC&author=Zimowska%2CW&author=Rayssiguier%2CY&author=Mazur%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="30."><p class="c-article-references__text" id="ref-CR30">Romani AM (2011) Cellular magnesium homeostasis. Arch Biochem Biophys 512:1–23</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.abb.2011.05.010" data-track-item_id="10.1016/j.abb.2011.05.010" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.abb.2011.05.010" aria-label="Article reference 30" data-doi="10.1016/j.abb.2011.05.010">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21640700" aria-label="PubMed reference 30">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXosFeisL4%3D" aria-label="CAS reference 30">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 30" href="http://scholar.google.com/scholar_lookup?&title=Cellular%20magnesium%20homeostasis&journal=Arch%20Biochem%20Biophys&doi=10.1016%2Fj.abb.2011.05.010&volume=512&pages=1-23&publication_year=2011&author=Romani%2CAM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="31."><p class="c-article-references__text" id="ref-CR31">Chi JT, Chang HY, Haraldsen G, Jahnsen FL, Troyanskaya OG, Chang DS, Wang Z, Rockson SG, Van de Rijn M, Botstein D, Brown PO (2003) Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci USA 100(19):10623–10628</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1073/pnas.1434429100" data-track-item_id="10.1073/pnas.1434429100" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1073%2Fpnas.1434429100" aria-label="Article reference 31" data-doi="10.1073/pnas.1434429100">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12963823" aria-label="PubMed reference 31">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXnslynsL4%3D" aria-label="CAS reference 31">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 31" href="http://scholar.google.com/scholar_lookup?&title=Endothelial%20cell%20diversity%20revealed%20by%20global%20expression%20profiling&journal=Proc%20Natl%20Acad%20Sci%20USA&doi=10.1073%2Fpnas.1434429100&volume=100&issue=19&pages=10623-10628&publication_year=2003&author=Chi%2CJT&author=Chang%2CHY&author=Haraldsen%2CG&author=Jahnsen%2CFL&author=Troyanskaya%2COG&author=Chang%2CDS&author=Wang%2CZ&author=Rockson%2CSG&author=Rijn%2CM&author=Botstein%2CD&author=Brown%2CPO"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="32."><p class="c-article-references__text" id="ref-CR32">Clark K, Langeslag M, Van Leeuwen B, Ran L, Ryazanov AG, Figdor CG, Moolenaar WH, Jalink K, Van Leeuwen FN (2006) TRPM7, a novel regulator of actomyosin contractility and cell adhesion. EMBO J 25(2):290–301</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/sj.emboj.7600931" data-track-item_id="10.1038/sj.emboj.7600931" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fsj.emboj.7600931" aria-label="Article reference 32" data-doi="10.1038/sj.emboj.7600931">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16407977" aria-label="PubMed reference 32">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28XntFSmsg%3D%3D" aria-label="CAS reference 32">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 32" href="http://scholar.google.com/scholar_lookup?&title=TRPM7%2C%20a%20novel%20regulator%20of%20actomyosin%20contractility%20and%20cell%20adhesion&journal=EMBO%20J&doi=10.1038%2Fsj.emboj.7600931&volume=25&issue=2&pages=290-301&publication_year=2006&author=Clark%2CK&author=Langeslag%2CM&author=Leeuwen%2CB&author=Ran%2CL&author=Ryazanov%2CAG&author=Figdor%2CCG&author=Moolenaar%2CWH&author=Jalink%2CK&author=Leeuwen%2CFN"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="33."><p class="c-article-references__text" id="ref-CR33">Wei C, Wang X, Chen M, Ouyang K, Song LS, Cheng H (2009) Calcium flickers steers cell migration. Nature 457:901–905</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1038/nature07577" data-track-item_id="10.1038/nature07577" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1038%2Fnature07577" aria-label="Article reference 33" data-doi="10.1038/nature07577">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19118385" aria-label="PubMed reference 33">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXht1ehtrs%3D" aria-label="CAS reference 33">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 33" href="http://scholar.google.com/scholar_lookup?&title=Calcium%20flickers%20steers%20cell%20migration&journal=Nature&doi=10.1038%2Fnature07577&volume=457&pages=901-905&publication_year=2009&author=Wei%2CC&author=Wang%2CX&author=Chen%2CM&author=Ouyang%2CK&author=Song%2CLS&author=Cheng%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="34."><p class="c-article-references__text" id="ref-CR34">Chen JP, Luan Y, You CX, Chen XH, Luo RC, Li R (2010) TRPM7 regulates the migration of human nasopharyngeal carcinoma cell by mediating Ca(2 +) influx. Cell Calcium 47(5):425–432</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1016/j.ceca.2010.03.003" data-track-item_id="10.1016/j.ceca.2010.03.003" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1016%2Fj.ceca.2010.03.003" aria-label="Article reference 34" data-doi="10.1016/j.ceca.2010.03.003">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20363498" aria-label="PubMed reference 34">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXmsVGrur4%3D" aria-label="CAS reference 34">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 34" href="http://scholar.google.com/scholar_lookup?&title=TRPM7%20regulates%20the%20migration%20of%20human%20nasopharyngeal%20carcinoma%20cell%20by%20mediating%20Ca%282%C2%A0%2B%29%20influx&journal=Cell%20Calcium&doi=10.1016%2Fj.ceca.2010.03.003&volume=47&issue=5&pages=425-432&publication_year=2010&author=Chen%2CJP&author=Luan%2CY&author=You%2CCX&author=Chen%2CXH&author=Luo%2CRC&author=Li%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="35."><p class="c-article-references__text" id="ref-CR35">Su LT, Liu W, Chen HC, Gonzàlez-Pagan O, Habas R, Runnels LW (2011) TRPM7 regulates polarized cell movements. Biochem J 434(3):513–521</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="10.1042/BJ20101678" data-track-item_id="10.1042/BJ20101678" data-track-value="article reference" data-track-action="article reference" href="https://doi.org/10.1042%2FBJ20101678" aria-label="Article reference 35" data-doi="10.1042/BJ20101678">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21208190" aria-label="PubMed reference 35">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXisVajuro%3D" aria-label="CAS reference 35">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 35" href="http://scholar.google.com/scholar_lookup?&title=TRPM7%20regulates%20polarized%20cell%20movements&journal=Biochem%20J&doi=10.1042%2FBJ20101678&volume=434&issue=3&pages=513-521&publication_year=2011&author=Su%2CLT&author=Liu%2CW&author=Chen%2CHC&author=Gonz%C3%A0lez-Pagan%2CO&author=Habas%2CR&author=Runnels%2CLW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="36."><p class="c-article-references__text" id="ref-CR36">Leidi M, Dellera F, Mariotti M, Maier JA (2011) High magnesium inhibits human osteoblast differentiation in vitro. Magnes Res 24:1–6</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21421455" aria-label="PubMed reference 36">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 36" href="http://scholar.google.com/scholar_lookup?&title=High%20magnesium%20inhibits%20human%20osteoblast%20differentiation%20in%20vitro&journal=Magnes%20Res&volume=24&pages=1-6&publication_year=2011&author=Leidi%2CM&author=Dellera%2CF&author=Mariotti%2CM&author=Maier%2CJA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="37."><p class="c-article-references__text" id="ref-CR37">Abed E, Martineau C, Moreau R (2011) Role of melastatin transient receptor potential 7 channels in the osteoblastic differentiation of murine MC3T3 cells. Calcif Tissue Int 88(3):246–253</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="noopener" data-track-label="10.1007/s00223-010-9455-z" data-track-item_id="10.1007/s00223-010-9455-z" data-track-value="article reference" data-track-action="article reference" href="https://link.springer.com/doi/10.1007/s00223-010-9455-z" aria-label="Article reference 37" data-doi="10.1007/s00223-010-9455-z">Article</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21207015" aria-label="PubMed reference 37">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXisVWmsLg%3D" aria-label="CAS reference 37">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 37" href="http://scholar.google.com/scholar_lookup?&title=Role%20of%20melastatin%20transient%20receptor%20potential%207%20channels%20in%20the%20osteoblastic%20differentiation%20of%20murine%20MC3T3%20cells&journal=Calcif%20Tissue%20Int&doi=10.1007%2Fs00223-010-9455-z&volume=88&issue=3&pages=246-253&publication_year=2011&author=Abed%2CE&author=Martineau%2CC&author=Moreau%2CR"> Google Scholar</a> </p></li></ol><p class="c-article-references__download u-hide-print"><a data-track="click" data-track-action="download citation references" data-track-label="link" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1007/s10456-011-9242-0?format=refman&flavour=references">Download references<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p></div></div></div></section></div><section data-title="Acknowledgments"><div class="c-article-section" id="Ack1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Ack1">Acknowledgments</h2><div class="c-article-section__content" id="Ack1-content"><p>This work was supported by FIRST-Università di Milano and ESA to JM.</p> <h3 class="c-article__sub-heading">Conflict of interest</h3> <p>The authors disclose no conflict of interest.</p> </div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Via GB Grassi, 74, 20157, Milano, Italy</p><p class="c-article-author-affiliation__authors-list">Erika Baldoli & Jeanette A. M. Maier</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Erika-Baldoli-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Erika Baldoli</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?dc.creator=Erika%20Baldoli" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Erika%20Baldoli" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Erika%20Baldoli%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Jeanette_A__M_-Maier-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Jeanette A. 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M. Maier</a>.</p></div></div></section><section data-title="Rights and permissions"><div class="c-article-section" id="rightslink-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="rightslink">Rights and permissions</h2><div class="c-article-section__content" id="rightslink-content"><p class="c-article-rights"><a data-track="click" data-track-action="view rights and permissions" data-track-label="link" href="https://s100.copyright.com/AppDispatchServlet?title=Silencing%20TRPM7%20mimics%20the%20effects%20of%20magnesium%20deficiency%20in%20human%20microvascular%20endothelial%20cells&author=Erika%20Baldoli%20et%20al&contentID=10.1007%2Fs10456-011-9242-0&copyright=Springer%20Science%2BBusiness%20Media%20B.V.&publication=0969-6970&publicationDate=2011-12-20&publisherName=SpringerNature&orderBeanReset=true">Reprints and permissions</a></p></div></div></section><section aria-labelledby="article-info" data-title="About this article"><div class="c-article-section" id="article-info-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="article-info">About this article</h2><div class="c-article-section__content" id="article-info-content"><div class="c-bibliographic-information"><div class="c-bibliographic-information__column"><h3 class="c-article__sub-heading" id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Baldoli, E., Maier, J.A.M. Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells. <i>Angiogenesis</i> <b>15</b>, 47–57 (2012). https://doi.org/10.1007/s10456-011-9242-0</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1007/s10456-011-9242-0?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Received<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2011-07-27">27 July 2011</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Accepted<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2011-12-08">08 December 2011</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Published<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2011-12-20">20 December 2011</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Issue Date<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2012-03">March 2012</time></span></p></li><li class="c-bibliographic-information__list-item c-bibliographic-information__list-item--full-width"><p><abbr title="Digital Object Identifier">DOI</abbr><span class="u-hide">: </span><span class="c-bibliographic-information__value">https://doi.org/10.1007/s10456-011-9242-0</span></p></li></ul><div data-component="share-box"><div 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