{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:36:34Z","timestamp":1783017394667,"version":"3.54.6"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"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":["81803129"],"award-info":[{"award-number":["81803129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We previously revealed the role of tanshinone IIA (TAN IIA) on endothelial cells and the impact of TAN IIA on the endothelial\u2010to\u2010mesenchymal transition in systemic sclerosis (SSc). In this study, we sought to further determine whether TAN IIA can directly act on the skin fibroblasts of scleroderma and look into its underlying anti\u2010fibrotic mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bleomycin was used to establish the SSc mouse model. After TAN IIA treatment, dermal thickness, type I collagen and hydroxyproline content were measured. Primary fibroblasts were acquired from SSc patients and cultured in vitro, and the effects of TAN IIA on proliferation, apoptosis and the cell cycle of fibroblasts were detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a bleomycin\u2010induced SSc model, we discovered that TAN IIA significantly improved skin thickness and collagen deposition, demonstrating a potent anti\u2010fibrotic action. TAN IIA inhibits the proliferation of skin fibroblasts derived from SSc patients by causing G2\/M cell cycle arrest and promoting apoptosis. Additionally, TAN IIA downregulated extracellular matrix gene transcription and collagen protein expression in skin fibroblasts in a dose\u2010gradient\u2010dependent manner. Furthermore, we showed how TAN IIA can reduce the activation of the transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2)\/Smad and mitogen\u2010activated protein kinase (MAPK)\/extracellular signal\u2010regulated kinase (ERK) pathways, which are important factors in SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In summary, these data suggest that TAN IIA can reduce SSc\u2010related skin fibrosis by modulating the TGF\u2010\u03b2\/Smad and MAPK\/ERK signalling pathways. More importantly, our results imply that TAN IIA can directly act on the skin fibroblasts of SSc, therefore, inhibiting fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1440-1681.13834","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T06:45:37Z","timestamp":1701413137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tanshinone <scp>IIA<\/scp> ameliorates the development of dermal fibrosis in systemic sclerosis"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6568-1540","authenticated-orcid":false,"given":"Ying","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Zhongshan Hospital, Fudan 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