{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:47:12Z","timestamp":1771512432506,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T00:00:00Z","timestamp":1459209600000},"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":["81270514, 31401210, and 31571455"],"award-info":[{"award-number":["81270514, 31401210, and 31571455"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20140955"],"award-info":[{"award-number":["BK20140955"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatic stellate cells (HSCs) are universally acknowledged to play a stimulative role in the pathogenesis of hepatic fibrosis and portal hypertension. HSCs when activated in response to liver injury are characterized with many changes, with HSC contraction being the most common cause of portal hypertension. Previous studies have shown that dihydroartemisinine (DHA) is a potential antifibrotic natural product by inducing HSC apoptosis, whereas the role of DHA in regulating HSC contraction and the mechanisms involved remain a riddle. Recent studies have emphasized on the importance of farnesoid X receptor (FXR) and sphingosine\u20101\u2010phosphate receptor 2 (S1PR2) in controlling cell contractility. This study showed that DHA strongly induced the mRNA and protein expression of FXR in LX\u20102 cells in a dose\u2010 and time\u2010dependent manner and inhibited HSC activation, implying a conceivable impact of DHA on HSC contraction. The gel contraction assays and fluorescence staining of actin cytoskeleton verified that DHA dose\u2010dependently limited contraction of collagen lattices and reorganization of actin stress fibers in LX\u20102 cells. DHA also decreased the phosphorylation of myosin light chain that is responsible for the contractile force of HSCs. Furthermore, gain\u2010 or loss\u2010of\u2010function analyses exhibited a FXR\u2010 and S1PR2\u2010dependent mechanism of inhibiting HSC contraction by DHA, and DHA decreased S1PR2 expression by modulating FXR activation. Subsequent work revealed that inhibition of both Ca<jats:sup>2+<\/jats:sup>\u2010dependent and Ca<jats:sup>2+<\/jats:sup>\u2010sensitization signaling transductions contributed to DHA\u2010induced HSC relaxation. In summary, these findings suggest that DHA could restrict HSC contraction through modulating FXR\/S1PR2 pathway\u2010mediated Ca<jats:sup>2+<\/jats:sup>\u2010dependent and Ca<jats:sup>2+<\/jats:sup>\u2010sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. \u00a9 2016 IUBMB Life 68(5):376\u2013387, 2016<\/jats:p>","DOI":"10.1002\/iub.1492","type":"journal-article","created":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T20:46:39Z","timestamp":1459457199000},"page":"376-387","source":"Crossref","is-referenced-by-count":30,"title":["Dihydroartemisinin restricts hepatic stellate cell contraction via an <scp>FXR\u2010S1PR2<\/scp>\u2010dependent mechanism"],"prefix":"10.1002","volume":"68","author":[{"given":"Wenxuan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Nanjing University of Chinese Medicine Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfeng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Nanjing University of Chinese Medicine Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Nanjing University of Chinese Medicine Nanjing Jiangsu Province China"},{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangjuan","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Nanjing University of Chinese Medicine Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shizhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Nanjing University of Chinese Medicine Nanjing Jiangsu Province China"},{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130246"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22203"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.07.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.08.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4194"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013955"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26939"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.04.207"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25780"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-014-3822-z"},{"key":"e_1_2_8_12_1","first-page":"1270","article-title":"Dihydroartemisinin suppresses inflammation and fibrosis in bleomycine\u2010induced pulmonary fibrosis in rats","volume":"8","author":"Yang D.","year":"2015","journal-title":"Int. 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