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Previous studies showed that prolonged treatment with praziquantel suppressed the development of liver fibrosis in mice with schistosomiasis. In this study, we investigated the potential mechanisms underlying the antifibrotic effects of praziquantel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>To avoid the effect of schistosomicidal activity of praziquantel against liver fibrosis induced by <jats:italic>Schistosoma japonicum<\/jats:italic> infection, we established a mouse model of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced liver fibrosis for in vivo studies and used TGF\u2010\u03b21\u2010stimulated human hepatic stellate cell line (LX\u20102) in addition to other fibroblast\u2010like cell line (MES13) and fibroblast cell line (NIH3T3) in vitro. Western blotting, immunohistochemistry, quantitative real\u2010time PCR, siRNA, and immunofluorescence staining were utilized to assess the expression of key molecules in liver fibrosis and the TGF\u2010\u03b2\/Smad pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Praziquantel significantly attenuated CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs) and expression of collagen matrix via enhancement of Smad7 expression, which were confirmed in LX\u20102, MES13, and NIH3T3 cells in vitro. In contrast, knockdown of Smad7 in LX\u20102 cells prevented praziquantel\u2010mediated inhibition of LX\u20102 cell activation and TGF\u2010\u03b21\u2010mediated collagen type I \u03b11 induction, revealing the critical role of Smad7 in the antifibrotic effect of praziquantel during liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>PZQ exhibited a strong efficacy against liver fibrosis by inhibiting activation of HSCs via Smad7 up\u2010regulation, suggesting potential broad utility in treatment of diseases characterized by liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14831","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T17:24:46Z","timestamp":1565803486000},"page":"4666-4680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Praziquantel ameliorates CCl<sub>4<\/sub>\u2010induced liver fibrosis in mice by inhibiting TGF\u2010\u03b2\/Smad signalling via up\u2010regulating Smad7 in hepatic stellate cells"],"prefix":"10.1111","volume":"176","author":[{"given":"Jinfeng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delong","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanci","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongkui","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"},{"name":"Department of Pathology Nanjing Children's Hospital  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6673-8591","authenticated-orcid":false,"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province Nanjing Medical University  Nanjing China"},{"name":"Department of Pathogen Biology and Immunology, Kangda College Nanjing Medical University  Lianyungang China"},{"name":"Key Laboratory of Infectious Diseases, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,29]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","first-page":"657","article-title":"Public health impact of schistosomiasis: Disease and mortality. 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