{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:50:05Z","timestamp":1792986605586,"version":"4.5.0"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2006,10,16]],"date-time":"2006-10-16T00:00:00Z","timestamp":1160956800000},"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":[[2007,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background and Aim:\u2002<\/jats:bold> The molecular mechanisms underlying the involvement of the renin\u2010angiotensin system in hepatic fibrosis are unclear. Recently, it was reported that a Rho kinase inhibitor prevented fibrosis of various tissues and that the Rho\/Rho kinase pathway was involved in the renin\u2010angiotensin system of vascular smooth muscle cells. In this study, the involvement of the Rho\/Rho kinase pathway on angiotensin II signaling in liver fibrogenesis and generation of steatosis was investigated.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Rats were fed a choline\u2010deficient\/L\u2010amino acid\u2010defined (CDAA) diet continuously and treated with a Rho kinase inhibitor, Y\u201027632, and an angiotensin II receptor blocker, TCV\u2010116. Liver histology and hepatic stellate cell activation were analyzed. Free radical production was detected by 4\u2010hydroxynonenal and 8\u2010hydroxy\u20102\u2032\u2010deoxyguanosine immunostaining and the expression of tumor necrosis factor\u2010\u03b1 was examined. Isolated hepatic stellate cells were pretreated with a Rho kinase inhibitor, Y\u201027632, or an angiotensin II receptor blocker, CV\u201011974, and stimulated with angiotensin II, and mRNA expression of transforming growth factor\u2010\u03b2 and \u03b1\u2010smooth muscle actin was analyzed.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Both the angiotensin II receptor blocker and the Rho kinase inhibitor improved fibrosis and steatosis of the liver in CDAA\u2010fed rats. The increase in the number of hepatocytes positive for 4\u2010hydroxynonenal and 8\u2010hydroxy\u20102\u2032\u2010deoxyguanosine in CDAA\u2010fed rats was significantly prevented by the angiotensin II receptor blocker and the Rho kinase inhibitor. The levels of tumor necrosis factor\u2010\u03b1 mRNA in the liver of CDAA\u2010fed rats were significantly increased and this increase was significantly inhibited by treatment with the angiotensin II receptor blocker and the Rho kinase inhibitor. mRNA expression of transforming growth factor\u2010\u03b2 and \u03b1\u2010smooth muscle actin stimulated by angiotensin II was also significantly suppressed by these two drugs.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> These results suggest that the Rho\/Rho kinase pathway is at least partly involved in the renin\u2010angiotensin system and plays an important role in hepatic fibrosis and steatosis.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2006.04735.x","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T06:09:35Z","timestamp":1161151775000},"page":"2022-2033","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Rho\/Rho kinase is a key enzyme system involved in the angiotensin II signaling pathway of liver fibrosis and steatosis"],"prefix":"10.1111","volume":"22","author":[{"given":"Kumi","family":"Kitamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Tada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Nakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Toda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Horikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kurita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tsunematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetsugu","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Hibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,10,2]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50018"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.020263"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2005.07.007"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020047"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06102-5"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20984"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.6.891"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.279.1.G7"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6346(01)00102-4"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705339"},{"key":"e_1_2_5_12_2","first-page":"140","article-title":"The role of vasoactive mediators in portal hypertension","volume":"6","author":"Garcia\u2010Pagan JC","year":"1995","journal-title":"Semin. 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