{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:46:56Z","timestamp":1790282816471,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,4,7]],"date-time":"2008-04-07T00:00:00Z","timestamp":1207526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\/Aims: <\/jats:bold> Liver fibrosis with any aetiology, induced by the transdifferentiation and proliferation of hepatic stellate cells (HSCs) to produce collagen, is characterized by progressive worsening in liver function, leading to a high incidence of death. We have recently reported that all\u2010<jats:italic>trans<\/jats:italic>\u2010retinoic acid (ATRA) suppresses the transdifferentiation and proliferation of lung fibroblasts and prevents radiation\u2010 or bleomycin\u2010induced lung fibrosis.<\/jats:p><jats:p><jats:bold>Methods: <\/jats:bold> We examined the impact of ATRA on carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced liver fibrosis. We performed histological examinations and quantitative measurements of transforming growth factor (TGF)\u2010\u03b21 and interleukin (IL)\u20106 in CCl<jats:sub>4<\/jats:sub>\u2010treated mouse liver tissues with or without the administration of ATRA, and investigated the effect of ATRA on the production of the cytokines in quiescent and activated HSCs.<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis was attenuated in histology by intraperitoneal administration of ATRA, and the overall survival rate at 12 weeks was 26.5% without ATRA (<jats:italic>n<\/jats:italic>=25), whereas it was 75.0% (<jats:italic>n<\/jats:italic>=24) in the treatment group (<jats:italic>P<\/jats:italic>=0.0187). <jats:italic>In vitro<\/jats:italic> studies disclosed that the administration of ATRA reduced (i) the production of TGF\u2010\u03b21, IL\u20106 and collagen from HSCs, (ii) TGF\u2010\u03b2\u2010dependent transdifferentiation of the cells and IL\u20106\u2010dependent cell proliferation and (iii) the activities of nuclear factor\u2010\u03baB p65 and p38mitogen\u2010activated protein kinase, which stimulate the production of TGF\u2010\u03b21 and IL\u20106, which could be the mechanism underlying the preventive effect of ATRA on liver fibrosis.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> Our findings indicate that ATRA ameliorates liver fibrosis. As the oral administration of the drug results in good compliance, ATRA could be a novel approach in the treatment of liver fibrosis.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2008.01745.x","type":"journal-article","created":{"date-parts":[[2010,8,27]],"date-time":"2010-08-27T13:27:49Z","timestamp":1282915669000},"page":"1217-1225","source":"Crossref","is-referenced-by-count":61,"title":["All\u2010<i>trans<\/i>\u2010retinoic acid ameliorates carbon tetrachloride\u2010induced liver fibrosis in mice through modulating cytokine production"],"prefix":"10.1111","volume":"28","author":[{"given":"Shigeo","family":"Hisamori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Tabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Kadokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kae","family":"Okoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Tabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Nagayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiharu","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,9,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2005.06.014"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-17554"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840080416"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-004-8167-7"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04361.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-006-9079-5"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.08.009"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20015"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.45.1.134"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705303"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200606-862OC"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00282.2005"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50063"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280611"},{"key":"e_1_2_6_17_2","first-page":"731","article-title":"Establishment of a new human cell line, LI90, exhibiting characteristics of hepatic Ito (fat\u2010storing) cells","volume":"72","author":"Murakami K","year":"1995","journal-title":"Lab Invest"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000225770.57219.b0"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5288"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6889com"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.4.601"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00169-6"},{"key":"e_1_2_6_23_2","first-page":"644","article-title":"Characterization of fat\u2010storing cell lines derived from normal and CCl4\u2010cirrhotic livers. 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