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Review the information below for assistance if you do not believe that you have done anything wrong.<div class="paragraphbreak" style="margin-top:0.5em"></div><div class="paragraphbreak" style="margin-top:0.5em"></div> <p>This block affects editing on all Wikimedia wikis. </p><p>The IP address or range 8.222.128.0/17 has been globally <a href="/wiki/Wikipedia:Blocking_policy" title="Wikipedia:Blocking policy">blocked</a> by <a href="/wiki/User:Jon_Kolbert" title="User:Jon Kolbert">‪Jon Kolbert‬</a> for the following reason(s): </p> <div style="padding:10px; background:var(--background-color-base, white); color:inherit; border:1px #666 solid;"> <p><a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/NOP" class="extiw" title="m:Special:MyLanguage/NOP">Open proxy/Webhost</a>: See the <a href="https://meta.wikimedia.org/wiki/WM:OP/H" class="extiw" title="m:WM:OP/H">help page</a> if you are affected </p> </div> <p>This block will expire on 15:12, 27 August 2028. Your current IP address is 8.222.208.146. </p> <div class="paragraphbreak" style="margin-top:0.5em"></div><div style="font-size: 16px;"> <p>Even while globally blocked, you will <i>usually</i> still be able to edit pages on <a href="https://meta.wikimedia.org/wiki/" class="extiw" title="m:">Meta-Wiki</a>. </p> </div> <div class="paragraphbreak" style="margin-top:0.5em"></div><div style="font-size: 16px;"> <p>If you believe you were blocked by mistake, you can find additional information and instructions in the <a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/No_open_proxies" class="extiw" title="m:Special:MyLanguage/No open proxies">No open proxies</a> global policy. Otherwise, to discuss the block please <a href="https://meta.wikimedia.org/wiki/Steward_requests/Global" class="extiw" title="m:Steward requests/Global">post a request for review on Meta-Wiki</a>. You could also send an email to the <a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/Stewards" class="extiw" title="m:Special:MyLanguage/Stewards">stewards</a> <a href="https://meta.wikimedia.org/wiki/Special:MyLanguage/VRT" class="extiw" title="m:Special:MyLanguage/VRT">VRT</a> queue at <kbd>stewards@wikimedia.org</kbd> including all above details. </p> </div> <p>Other useful links: <a href="https://meta.wikimedia.org/wiki/Global_blocks" class="extiw" title="m:Global blocks">Global blocks</a> · <a href="/wiki/Help:I_have_been_blocked" title="Help:I have been blocked">Help:I have been blocked</a> </p> </div></li></ul><hr /> <div id="viewsourcetext">You can view and copy the source of this page:</div><textarea readonly="" accesskey="," id="wpTextbox1" cols="80" rows="25" style="" class="mw-editfont-monospace" lang="en" dir="ltr" name="wpTextbox1">== Pharmacodynamics == ;HSGAGs: Endogenous heparin is localized and stored in secretory granules of [[mast cell]]s. [[Histamine]] that is present within the granules is protonated (H<sub>2</sub>A<sup>2+</sup>) at pH within granules (5.2–6.0), thus it is believed that heparin, which is highly negatively charged, functions to electrostatically retain and store histamine.<ref name=Rabenstein>{{cite journal |author=Rabenstein DL. |title=Heparin and heparan sulfate: structure and function |journal=Natural Product Reports |volume=19 |issue=3 |pages=312–31 |year=2002 |pmid=12137280 |doi=10.1039/B100916H }}</ref> In the clinic, heparin is administered as an anticoagulant and is also the first line choice for thromboembolic diseases.<ref>{{cite journal |vauthors=Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW |title=The anticoagulant activation of antithrombin by heparin. |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=94 |issue=26 |pages=14683–88 |year=1997 |pmid=9405673 | doi=10.1073/pnas.94.26.14683 |pmc=25092|bibcode=1997PNAS...9414683J |doi-access=free }}</ref><ref>{{cite book |last=Rodén |first=L. |editor-first=DA |editor-last=Lane |title=Heparin: Chemical and Biological Properties, Clinical Applications |publisher=CRC Press, Inc. |year=1989 |page=1}}</ref> Heparan sulfate (HS) has numerous biological activities and functions, including cell adhesion, regulation of cell growth and proliferation, developmental processes, cell surface binding of lipoprotein lipase and other proteins, angiogenesis, viral invasion, and tumor metastasis.<ref name=Rabenstein /> CSGAGs interact with heparin binding proteins, specifically dermatan sulfate interactions with fibroblast growth factor FGF-2 and FGF-7 have been implicated in cellular proliferation and wound repair<ref name=Trowbridge>{{cite journal |vauthors=Trowbridge JM, Gallo RL | title=Dermatan sulfate: new functions from an old glycosaminoglycan | journal=Glycobiology | year=2002 | pages=117R–125R | volume=12 | issue=9 | pmid=12213784 | doi=10.1093/glycob/cwf066| doi-access=free }}</ref> while interactions with hepatic growth factor/scatter factor (HGF/SF) activate the HGF/SF signaling pathway ([[c-Met]]) through its receptor. CSGAGs are important in providing support and adhesiveness in bone, skin, and cartilage. Other biological functions for which CSGAGs are known to play critical functions in include inhibition of axonal growth and regeneration in CNS development, roles in brain development, neuritogenic activity, and pathogen infection.<ref>{{cite journal |vauthors=Sugahara K, Mikami T, Uyama T, Mizuguchi S, Nomura K, Kitagawa H | title=Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate. | journal=Current Opinion in Structural Biology | year=2003 | pages=612–20 | volume=13 | issue=5 | pmid=14568617 | doi=10.1016/j.sbi.2003.09.011}}</ref> ;Keratan sulfates:One of the main functions of the third class of GAGs, keratan sulfates, is the maintenance of tissue hydration.<ref name="Funderburgh3" /> Keratan sulfates are in the bone, cartilage, and the cornea of the eye.<ref name=":0" /> Within the normal cornea, dermatan sulfate is fully hydrated whereas keratan sulfate is only partially hydrated suggesting that keratan sulfate may behave as a dynamically controlled buffer for hydration.<ref name=Funderburgh3>{{cite journal | author=Funderburgh, JL. | title=Keratan sulfate: structure, biosynthesis, and function. | journal=Glycobiology | year=2000 | pages=951–58 | volume=10 | issue=10 | pmid=11030741 | doi=10.1093/glycob/10.10.951| doi-access=free }}</ref> In disease states such as [[macular corneal dystrophy]], in which GAGs levels such as KS are altered, loss of hydration within the corneal stroma is believed to be the cause of corneal haze, thus supporting the long-held hypothesis that corneal transparency is dependent on proper levels of keratan sulfate. Keratan sulfate GAGs are found in many other tissues besides the cornea, where they are known to regulate [[macrophage]] adhesion, form barriers to [[neurite]] growth, regulate [[embryo implantation]] in the endometrial uterine lining during menstrual cycles, and affect the motility of corneal endothelial cells.<ref name=Funderburgh3 /> In summary, KS plays an anti-adhesive role, which suggests very important functions of KS in cell motility and attachment as well as other potential biological processes. '''Dermatan sulfates''' Dermatan sulfates function in the skin, tendons, blood vessels, and heart valves.<ref name=":0" /> ;Hyaluronic acid: [[Hyaluronic acid]] is a major component of [[Synovial membrane|synovial tissues]] and [[Synovial fluid|fluid]], as well as the [[ground substance]] of other connective tissues. Hyaluronic acid binds cells together, lubricates joints, and helps maintain the shape of the eyeballs.<ref name=":0">{{Cite book|title=Principles of anatomy & physiology|last=Tortora, Gerard J.|others=Derrickson, Bryan|isbn=978-1-118-34500-9|edition=14th|location=Danvers, MA|oclc=871018672|date=2013-12-31|url-access=registration|url=https://archive.org/details/principlesofanat0000tort}}</ref> The [[viscoelasticity]] of hyaluronic acid makes it ideal for lubricating joints and surfaces that move along each other, such as cartilage. A solution of hyaluronic acid under low [[shear stress]] has a much higher viscosity than while under high shear stress.<ref name="Laurent">{{cite journal|vauthors=Laurent TC, Laurent UB, Fraser JR|year=1996|title=The structure and function of hyaluronan: An overview.|journal=Immunology and Cell Biology|volume=74|issue=2|pages=A1-7|doi=10.1038/icb.1996.32|pmid=8724014}}</ref> [[Hyaluronidase]], an enzyme produced by white blood cells, sperms cells, and some bacteria, breaks apart the hyaluronic acid, causing the solution to become more liquid.<ref name=":0" /> :''In vivo'', hyaluronic acid forms randomly kinked coils that entangle to form a hyaluronan network, slowing diffusion and forming a diffusion barrier that regulates transport of substances between cells. For example, hyaluronan helps partition plasma proteins between vascular and extravascular spaces, which affects solubility of macromolecules in the interstitium, changes chemical equilibria, and stabilizes the structure of collagen fibers.<ref name="Laurent" /> :Other functions include matrix interactions with hyaluronan binding proteins such as hyaluronectin, glial hyaluronan binding protein, brain enriched hyaluronan binding protein, [[collagen VI]], [[TSG-6]], and [[inter-alpha-trypsin inhibitor]]. Cell surface interactions involving hyaluronan are its well-known coupling with [[CD44]], which may be related to tumor progression, and also with RHAMM ([[Hyaluronan-mediated motility receptor]]), which has been implicated in developmental processes, tumor metastasis, and pathological reparative processes. :Fibroblasts, mesothelial cells, and certain types of stem cells surround themselves in a [[Glycocalyx|pericellular "coat"]], part of which is constructed from hyaluronan, in order to shield themselves from bacteria, red blood cells, or other matrix molecules. For example, in regard to stem cells, hyaluronan, along with chondroitin sulfate, helps to form the [[stem cell niche]]. Stem cells are protected from the effects of growth factors by a shield of hyaluronan and minimally sulfated chondroitin sulfate. During progenitor division, the daughter cell moves outside of this pericellular shield where it can then be influenced by growth factors to differentiate even further. </textarea><div class="templatesUsed"></div><p id="mw-returnto">Return to <a href="/wiki/Glycosaminoglycan" title="Glycosaminoglycan">Glycosaminoglycan</a>.</p> <noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?type=1x1" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/wiki/Glycosaminoglycan">https://en.wikipedia.org/wiki/Glycosaminoglycan</a>"</div></div> <div id="catlinks" class="catlinks catlinks-allhidden" data-mw="interface"></div> </div> </main> </div> <div class="mw-footer-container"> <footer id="footer" class="mw-footer" > <ul id="footer-info"> </ul> <ul id="footer-places"> <li id="footer-places-privacy"><a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Privacy_policy">Privacy policy</a></li> <li id="footer-places-about"><a href="/wiki/Wikipedia:About">About Wikipedia</a></li> <li id="footer-places-disclaimers"><a href="/wiki/Wikipedia:General_disclaimer">Disclaimers</a></li> <li id="footer-places-contact"><a href="//en.wikipedia.org/wiki/Wikipedia:Contact_us">Contact Wikipedia</a></li> <li id="footer-places-wm-codeofconduct"><a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Universal_Code_of_Conduct">Code of Conduct</a></li> <li id="footer-places-developers"><a href="https://developer.wikimedia.org">Developers</a></li> <li id="footer-places-statslink"><a href="https://stats.wikimedia.org/#/en.wikipedia.org">Statistics</a></li> <li id="footer-places-cookiestatement"><a href="https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Cookie_statement">Cookie statement</a></li> <li id="footer-places-mobileview"><a href="//en.m.wikipedia.org/w/index.php?title=Glycosaminoglycan&action=edit&section=5&mobileaction=toggle_view_mobile" class="noprint stopMobileRedirectToggle">Mobile view</a></li> </ul> <ul id="footer-icons" class="noprint"> <li id="footer-copyrightico"><a href="https://wikimediafoundation.org/" class="cdx-button cdx-button--fake-button cdx-button--size-large cdx-button--fake-button--enabled"><img src="/static/images/footer/wikimedia-button.svg" width="84" height="29" alt="Wikimedia Foundation" loading="lazy"></a></li> <li id="footer-poweredbyico"><a href="https://www.mediawiki.org/" class="cdx-button cdx-button--fake-button cdx-button--size-large cdx-button--fake-button--enabled"><img src="/w/resources/assets/poweredby_mediawiki.svg" alt="Powered by MediaWiki" width="88" height="31" loading="lazy"></a></li> </ul> </footer> </div> </div> </div> <div class="vector-settings" id="p-dock-bottom"> <ul></ul> </div><script>(RLQ=window.RLQ||[]).push(function(){mw.config.set({"wgHostname":"mw-web.codfw.canary-84779d6bf6-wmcb5","wgBackendResponseTime":193,"wgPageParseReport":{"limitreport":{"cputime":"0.049","walltime":"0.065","ppvisitednodes":{"value":418,"limit":1000000},"postexpandincludesize":{"value":17740,"limit":2097152},"templateargumentsize":{"value":6556,"limit":2097152},"expansiondepth":{"value":9,"limit":100},"expensivefunctioncount":{"value":0,"limit":500},"unstrip-depth":{"value":0,"limit":20},"unstrip-size":{"value":469,"limit":5000000},"entityaccesscount":{"value":0,"limit":400},"timingprofile":["100.00% 45.169 1 -total"," 99.85% 45.102 2 Template:Blocked_text"," 41.33% 18.669 1 Template:Colocationwebhost"," 39.37% 17.783 2 Template:Replace"," 37.23% 16.817 1 Template:Hidden"," 15.89% 7.176 1 Template:Tlx"," 15.21% 6.871 1 Template:Hidden_begin"," 2.44% 1.103 1 MediaWiki:Wikimedia-globalblocking-blockedtext-mistake"," 2.38% 1.075 1 Template:Hidden_end"," 2.25% 1.016 1 MediaWiki:Wikimedia-globalblocking-blockedtext-mistake-email-steward"]},"scribunto":{"limitreport-timeusage":{"value":"0.010","limit":"10.000"},"limitreport-memusage":{"value":1043265,"limit":52428800}},"cachereport":{"origin":"mw-web.codfw.canary-84779d6bf6-wmcb5","timestamp":"20241124011109","ttl":2592000,"transientcontent":false}}});});</script> </body> </html>