{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T09:52:49Z","timestamp":1784973169874,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,9,25]],"date-time":"2009-09-25T00:00:00Z","timestamp":1253836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold>To investigate whether fenretinide, a clinically proved apoptosis\u2010inducing chemopreventive agent in tumor cells, can induce apoptosis in hepatic stellate cells (HSCs) and resolve hepatic fibrosis.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold>CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis in mice and rat activated hepatic stellate cells (HSC\u2010T6) as well as hepatocytes (BRL\u20103A) were studied.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold>The duplex staining of proliferating cell nuclear antigen and \u03b1\u2010 smooth muscle actin or terminal deoxynucleotidyl transferase\u2010mediated deoxyuridine triphosphate nick\u2010end labeling and \u03b1\u2010 smooth muscle actin demonstrated that fenretinide executed its anti\u2010fibrosis effect in liver by inducing apoptosis rather than inhibiting proliferation of HSCs, while it had no apparently apoptotic effect on hepatocytes. Fenretinide could elicit apoptosis of HSC\u2010T6<jats:italic>in vitro<\/jats:italic>at the concentration range from 0.5 to 5\u2003\u00b5M, but at higher concentrations \u22655\u2003\u00b5M was required to induce apoptosis in hepatocytes (BRL\u20103A).<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold>Further studies using malondialdehyde measurement, Western blot, antioxidant, inhibitors for p53, caspase 8 and 9 \u2013 as well as anti\u2010Fas neutralizing antibody \u2013 have shown that in HSC\u2010T6, fenretinide\u2010induced apoptosis involves a reactive oxygen species (ROS)\u2010generated, P53\u2010independent, mitochondria\u2010associated intrinsic pathway, whereas in hepatocytes (BRL\u20103A), a ROS\u2010generated, P53\u2010dependent, Fas\u2010related extrinsic pathway is triggered only at high concentration.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2009.00562.x","type":"journal-article","created":{"date-parts":[[2009,9,25]],"date-time":"2009-09-25T17:06:20Z","timestamp":1253898380000},"page":"1229-1247","source":"Crossref","is-referenced-by-count":9,"title":["Fenretinide stimulates the apoptosis of hepatic stellate cells and ameliorates hepatic fibrosis in mice"],"prefix":"10.1111","volume":"39","author":[{"given":"Jin","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Sheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue Qing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Ling","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199306243282508"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0920103"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051073"},{"key":"e_1_2_6_5_2","first-page":"193","article-title":"Rat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture","volume":"24","author":"Rockey DC","year":"1992","journal-title":"J Submicrosc Cytol Pathol"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.27188"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700116"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64994-2"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00474.2002"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.10.003"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00361-6"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI992"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2003.10.020"},{"key":"e_1_2_6_14_2","first-page":"1265","article-title":"CD95\/CD95L\u2010mediated apoptosis of the hepatic stellate cell. 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