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Its essential characteristics are disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. However, the role of ferroptosis in liver fibrosis remains poorly understood. In this study, we attempted to investigate the effect of artemether (ART) on ferroptosis in hepatic fibrosis and to further clarify the possible mechanisms. Our data showed that ART treatment markedly attenuated liver injury and reduced fibrotic scar formation in the mouse model of liver fibrosis. Moreover, experiments <jats:italic>in vitro<\/jats:italic> also confirmed that ART treatment significantly decreased expression of hepatic stellate cell (HSC) activation markers. Interestingly, HSCs treated by ART presented morphological features of ferroptosis. Furthermore, ART remarkably triggered ferroptosis by promoting the accumulation of iron and lipid peroxides, whereas inhibition of ferroptosis by specific inhibitor ferrostatin\u20101 (Fer\u20101) completely abolished ART\u2010induced antifibrosis effect. More importantly, our discovery determined that tumor suppressor P53 was an upstream molecule in the facilitation of ART\u2010induced HSC ferroptosis. Conversely, knockdown of P53 by siRNA evidently blocked ART\u2010induced HSC ferroptosis in turn exacerbated liver fibrosis. Overall, our findings revealed that P53\u2010dependent induction of ferroptosis is necessary for ART to ameliorate CCl<jats:sub>4<\/jats:sub>\u2010induced hepatic fibrosis and inhibit HSC activation. \u00a9 2018 IUBMB Life, 71(1):45\u201356, 2019<\/jats:p>","DOI":"10.1002\/iub.1895","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T20:35:41Z","timestamp":1539635741000},"page":"45-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["P53\u2010dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride\u2010induced liver fibrosis and hepatic stellate cell activation"],"prefix":"10.1002","volume":"71","author":[{"given":"Ling","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangjuan","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Saint Louis University  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7092-7843","authenticated-orcid":false,"given":"Shizhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy, Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5604\/16652681.1226814"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2016.07.001"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.03.039"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10790"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28948"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.157420"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26592"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.92"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.10.498"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"issue":"8","key":"e_1_2_8_12_1","first-page":"779","article-title":"Ferroptosis, a new form of cell death relevant to the medical treatment of cancer","volume":"30","author":"Lachaier E.","year":"2014","journal-title":"Med. 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