{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:02:43Z","timestamp":1779134563520,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,4,18]],"date-time":"2006-04-18T00:00:00Z","timestamp":1145318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold> Previous studies have shown that the renin\u2010angiotensin system (RAS) plays an important role in the pathogenesis of hepatic fibrosis, and blockers of the RAS may be active as an antifibrogenic goal. However, the potential role of RAS inhibition on expression transforming growth factor (TGF)\u2010\u03b2\u2010Smads in hepatic fibrosis remains unknown. The aim of this study was to investigate the effect and mechanism of an angiotensin\u2010converting enzyme inhibitor (perindopril) and an angiotensin II receptor blocker (valsartan) on TGF\u2010\u03b21 and TGF receptor II (TRII) mRNA, Smad3 and Smad7 in fibrotic hepatic livers in rats.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Sixty Wistar rats were randomly divided into four study groups (<jats:italic>n<\/jats:italic>\u2003=\u200315 for each group), including normal controls, hepatic fibrosis models, and two treated groups with either perindopril or valsartan, starting from the fourth week after being exposed to carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) for 4\u2003weeks. The levels of TGF\u2010\u03b2 and TRII mRNA in liver tissue were analyzed by RT\u2010PCR. The expressions of TGF\u2010\u03b21, Smad3 and Smad7 in liver tissues were evaluated by immunohistochemistry. The liver histopathology was examined by hematoxylin and eosin (HE) staining and by electron microscopy, respectively. The liver function and serum hyaluronic acid were also assayed by biochemistry and radioimmunoassay.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Compared with the hepatic fibrosis models, the levels of TGF\u2010\u03b21, TRII mRNA and the expression Smad3 significantly decreased in the two treated groups, and the expression of Smad7 was significantly increased in the liver of rats treated with perindopril or valsartan (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05 or <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01). The histological changes and ultrastructure of fibrotic liver, liver function and hyaluronic acid also remarkably improved in the treated rats.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> The angiotensin\u2010converting enzyme inhibitors perindopril and valsartan have a protective effect on liver injury and can ameliorate hepatic fibrosis in rats induced by CCl<jats:sub>4<\/jats:sub>. The mechanisms may be associated with their effects of down\u2010regulating TGF\u2010\u03b21, TRII mRNA and smad3, and up\u2010regulating Smad7.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2006.04331.x","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T01:27:58Z","timestamp":1145582878000},"page":"1250-1256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effects of perindopril and valsartan on expression of transforming growth factor\u2010\u03b2\u2010Smads in experimental hepatic fibrosis in rats"],"prefix":"10.1111","volume":"21","author":[{"given":"Wei","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiling","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuojiong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,10]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.36561"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/snep.2001.26795"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00104-6"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.10.093"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02656-4"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840200213"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000069792"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.28231"},{"key":"e_1_2_5_10_2","first-page":"583","article-title":"The expression of AT1 receptor on hepatic stellate cells in rat fibrosis induced by CCl4","volume":"114","author":"Wei H","year":"2001","journal-title":"Chin. 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