{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:04:24Z","timestamp":1790712264665,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,4,29]],"date-time":"2017-04-29T00:00:00Z","timestamp":1493424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Of the circa 40 cytokines of the TGF-\u03b2 superfamily, around a third are currently known to bind to heparin and heparan sulphate. This includes TGF-\u03b21, TGF-\u03b22, certain bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), as well as GDNF and two of its close homologues. Experimental studies of their heparin\/HS binding sites reveal a diversity of locations around the shared cystine-knot protein fold. The activities of the TGF-\u03b2 cytokines in controlling proliferation, differentiation and survival in a range of cell types are in part regulated by a number of specific, secreted BMP antagonist proteins. These vary in structure but seven belong to the CAN or DAN family, which shares the TGF-\u03b2 type cystine-knot domain. Other antagonists are more distant members of the TGF-\u03b2 superfamily. It is emerging that the majority, but not all, of the antagonists are also heparin binding proteins. Any future exploitation of the TGF-\u03b2 cytokines in the therapy of chronic diseases will need to fully consider their interactions with glycosaminoglycans and the implications of this in terms of their bioavailability and biological activity.<\/jats:p>","DOI":"10.3390\/molecules22050713","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T11:37:20Z","timestamp":1493725040000},"page":"713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Heparin, Heparan Sulphate and the TGF-\u03b2 Cytokine Superfamily"],"prefix":"10.3390","volume":"22","author":[{"given":"Chris","family":"Rider","sequence":"first","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Mulloy","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2008.323","article-title":"Roles of TGF-beta family signaling in stem cell renewal and differentiation","volume":"19","author":"Watabe","year":"2009","journal-title":"Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.autrev.2016.07.007","article-title":"Revisiting the regulatory roles of the TGF-beta family of cytokines","volume":"15","author":"Fujio","year":"2016","journal-title":"Autoimmun. 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