{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:19:43Z","timestamp":1791821983798,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Liver fibrosis is a wound\u2010healing reaction that eventually leads to cirrhosis. Hydronidone is a new pyridine derivative with the potential to treat liver fibrosis. In this study, we explored the antifibrotic effects of hydronidone and its potential mode of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The anti\u2010hepatic fibrosis effects of hydronidone were studied in carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010 and 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine (DDC)\u2010 induced animal liver fibrosis. The antifibrotic mechanisms of hydronidone were investigated in hepatic stellate cells (HSCs). The antifibrotic effect of hydronidone was further tested after Smad7 knockdown in HSCs in mouse models of fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In animal models, hydronidone attenuated liver damage and collagen accumulation, and reduced the expression of fibrosis\u2010related genes. Hydronidone decreased the expression of fibrotic genes in HSCs. Impressively, hydronidone significantly upregulated Smad7 expression and promoted the degradation of transforming growth factor \u03b2 receptor I (TGF\u03b2RI) in HSCs and thus inhibited the TGF\u03b2\u2010Smad signalling pathway. Specific knockdown of Smad7 in HSCs in vivo blocked the antifibrotic effect of hydronidone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hydronidone ameliorates liver fibrosis by inhibiting HSCs activation via Smad7\u2010mediated TGF\u03b2RI degradation. Hydronidone is a potential drug candidate for the treatment of liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15715","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T06:31:36Z","timestamp":1693290696000},"page":"2523-2537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Hydronidone ameliorates liver fibrosis by inhibiting activation of hepatic stellate cells via Smad7\u2010mediated degradation of <scp>TGF\u03b2RI<\/scp>"],"prefix":"10.1111","volume":"43","author":[{"given":"Xianjun","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuecheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongshang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Huaian First People's Hospital, Nanjing Medical University  Huaian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Diseases Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Ye","sequence":"additional","affiliation":[{"name":"Continent Pharmaceuticals Co., Ltd.  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