{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:56:13Z","timestamp":1790758573222,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T00:00:00Z","timestamp":1598140800000},"content-version":"am","delay-in-days":359,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T00:00:00Z","timestamp":1567123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM85456"],"award-info":[{"award-number":["R01GM85456"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000082","name":"Division of Graduate Education","doi-asserted-by":"publisher","award":["DGE 1144804"],"award-info":[{"award-number":["DGE 1144804"]}],"id":[{"id":"10.13039\/100000082","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The anti\u2010malaria drug artesunate and other chemical analogs of artemisinin have demonstrated cytostatic and cytotoxic effects in bacterial and cancer cells. Artemisinin\u2010derived compounds have also been demonstrated to attenuate fibrosis in preclinical animal models, but the mechanisms by which this inhibition occurs are not well\u2010understood. We investigated the effects of artesunate on the emergence of the myofibroblast, which is causally implicated in pro\u2010fibrotic pathologies. CRL\u20102097 human dermal fibroblasts were analyzed for protein and transcript expression after treatment with artesunate to analyze fibroblast activation. Proliferation and apoptosis were also evaluated following treatment with artesunate in this cell line. Treatment of human dermal fibroblasts with artesunate antagonized fibroblast activation and pro\u2010fibrotic extracellular matrix (ECM) deposition, both at basal culture conditions and when cultured in the presence of exogenous transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21), a major pro\u2010fibrotic cytokine. Artesunate\u2010treated fibroblasts also demonstrated decreased proliferation and increased apoptosis. Transcript analysis by quantitative real\u2010time polymerase chain reaction demonstrated that artesunate downregulated expression of pro\u2010fibrotic genes including canonical myofibroblast markers, ECM genes, and several TGF\u2010\u03b2 receptors and ligands, and upregulated expression of cell cycle inhibitors and matrix\u2010metalloproteinases. Together, these data demonstrate that artesunate antagonizes fibroblast activation and decreases expression of pro\u2010fibrotic genes, while also promoting myofibroblast apoptosis, suggesting that these mechanisms may be responsible in part for the anti\u2010fibrotic effects of artesunate described previously.<\/jats:p>","DOI":"10.1002\/cbin.11220","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T04:43:48Z","timestamp":1566535428000},"page":"1317-1322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Artesunate inhibits myofibroblast formation via induction of apoptosis and antagonism of pro\u2010fibrotic gene expression in human dermal fibroblasts"],"prefix":"10.1002","volume":"43","author":[{"given":"Sara A.","family":"Larson","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology Worcester Polytechnic Institute  100 Institute Road Worcester Massachusetts 01609 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-4294","authenticated-orcid":false,"given":"David M.","family":"Dolivo","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Worcester Polytechnic Institute  100 Institute Road Worcester Massachusetts 01609 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Dominko","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Worcester Polytechnic Institute  100 Institute Road Worcester Massachusetts 01609 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,30]]},"reference":[{"issue":"20","key":"e_1_2_9_1_2_1","first-page":"3785","article-title":"Role of Fas, FasL and caspase\u20103 in artesunate\u2010induced apoptosis of human embryonic lung fibroblasts","volume":"15","author":"Chang\u2010ming 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human cultured airway smooth muscle cell proliferation","volume":"50","author":"Tan SS","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"e_1_2_9_1_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3500"},{"key":"e_1_2_9_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(00)00002-6"},{"key":"e_1_2_9_1_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31487"}],"container-title":["Cell Biology 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