{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:39:36Z","timestamp":1789886376002,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:00:00Z","timestamp":1493683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Transforming growth factor\u2010beta (TGF\u2010\u03b2) plays a central role in the pathogenesis of oral submucous fibrosis (OSF). Thrombin is a key player in tissue repair, inflammation, and fibrosis after injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Effects of thrombin on activated\u2010TGF\u2010\u03b21 levels, Smad3 phosphorylation, and connective tissue growth factor (CTGF\/CCN2) synthesis in primary human buccal mucosal fibroblasts (BMFs) were assessed by enzyme\u2010linked immunosorbent assay or Western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thrombin and protease\u2010activated receptor\u20101 (PAR\u20101) agonist induced TGF\u2010\u03b21 activation and Smad3 phosphorylation. Pretreatment with TGF\u2010\u03b2\u2010neutralizing antibody completely inhibited thrombin\u2010induced CCN2 synthesis. Neutralizing antibodies to integrin \u03b1v, \u03b21, \u03b1v\u03b23, \u03b1v\u03b25, and Rho\u2010associated coiled\u2010coil forming protein kinase (ROCK) inhibitor Y27632 completely blocked thrombin\u2010induced TGF\u2010\u03b21 activation, Smad3 phosphorylation, and CCN2 synthesis. Epigallocatechin\u20103\u2010gallate (EGCG) dose\u2010dependently inhibited thrombin\u2010induced TGF\u2010\u03b21 activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Thrombin induces \u03b1v\u03b21, \u03b1v\u03b23, and \u03b1v\u03b25 integrins\u2010mediated TGF\u2010\u03b21 activations via ROCK signaling. EGCG inhibits thrombin\u2010induced CCN2 synthesis in BMFs by suppressing latent TGF\u2010\u03b21 activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.24791","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T12:42:07Z","timestamp":1493728927000},"page":"1436-1445","source":"Crossref","is-referenced-by-count":28,"title":["Activation of transforming growth factor\u2010\u03b21 by thrombin via integrins \u03b1v\u03b21, \u03b1v\u03b23, and \u03b1v\u03b25 in buccal fibroblasts: Suppression by epigallocatechin\u20103\u2010gallate"],"prefix":"10.1002","volume":"39","author":[{"given":"Jenny Zwei\u2010Chieng","family":"Chang","sequence":"first","affiliation":[{"name":"School of Dentistry College of Medicine, National Taiwan University Taipei Taiwan"},{"name":"Department of Dentistry National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ping","family":"Hsieh","sequence":"additional","affiliation":[{"name":"School of Dentistry College of Medicine, National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Hsin","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Dentistry College of Medicine, National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin\u2010Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Dentistry College of Medicine, National Taiwan University Taipei Taiwan"},{"name":"Department of Dentistry National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Yen\u2010Ping","family":"Kuo","sequence":"additional","affiliation":[{"name":"School of Dentistry College of Medicine, National Taiwan University Taipei 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