{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:02:41Z","timestamp":1792623761259,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81302567"],"award-info":[{"award-number":["81302567"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601435"],"award-info":[{"award-number":["81601435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873882"],"award-info":[{"award-number":["81873882"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Iguratimod (T\u2010614), exerting a powerful anti\u2010inflammatory ability, has therapeutic efficacy in multiple autoimmune diseases. However, the effect of T\u2010614 on systemic sclerosis (SSc) is unclear. Here, we investigate the effect and molecular mechanism of T\u2010614 in experimental SSc models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In vitro, cultured dermal fibroblasts from four SSc patients were subjected to different doses of T\u2010614 in the presence or absence of TGF\u2010\u03b21\u00a0stimulation. Cell proliferation, apoptosis and migration were determined by CCK\u20108, flow cytometry and transwell assay, respectively. Fibrosis markers and smad signalling pathway\u2010related proteins were detected by immunoblotting and immunofluorescence. In vivo, a bleomycin\u2010induced SSc mouse model was used to evaluate the effect of T\u2010614 on skin fibrosis. Pathological changes in skin tissues were evaluated by HE, Masson staining and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the study, we found T\u2010614 inhibited TGF\u2010\u03b21\u2010induced cell proliferation, migration and promoted apoptosis in a dose\u2010dependent manner (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). T\u2010614 partially reversed TGF\u2010\u03b21\u2010induced upregulation of fibrosis markers and phosphorylation of smad2 and smad3 and blocked p\u2010Smad3 nuclear translocation (all <jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.05), suggesting T\u2010614\u00a0may inhibit dermal fibroblasts activation by regulating TGF\u2010\u03b21\/smad pathway. In vivo experiments, T\u2010614 alleviated skin thickness in bleomycin\u2010induced SSc mice (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). The expression of fibrosis markers and the infiltration of macrophages in skin tissue were significantly decreased after T\u2010614 treatment (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our preliminary data indicated T\u2010614 inhibited dermal fibroblasts activation and skin fibrosis at least partly by regulating TGF\u2010\u03b21\/smad pathway in experimental SSc models and may be a promising therapeutic agent for SSc.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13791","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T12:04:22Z","timestamp":1650456262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Iguratimod inhibits skin fibrosis by regulating TGF\u2010\u03b21\/Smad signalling pathway in systemic sclerosis"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-2324","authenticated-orcid":false,"given":"Xi","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Clinical Immunology Research Center Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haina","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The Second Xiangya Hospital Central South University  Changsha China"},{"name":"Clinical Immunology Research Center Central South University  Changsha China"},{"name":"Department of Rheumatology and Immunology The First People\u2019s Hospital of Changde City  Changde 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