{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:09:41Z","timestamp":1790719781790,"version":"4.1.0"},"reference-count":39,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,5,1]]},"abstract":"<jats:p>The effect of liver growth stimulation [using the rodent PXR (pregnane X receptor) activator PCN (pregnenolone-16\u03b1-carbonitrile)] in rats chronically treated with carbon tetrachloride to cause repeated hepatocyte necrosis and liver fibrogenesis was examined. PCN did not inhibit the hepatotoxicity of carbon tetrachloride. However, transdifferentiation of hepatic stellate cells and the extent of fibrosis caused by carbon tetrachloride treatment was significantly inhibited by PCN in vivo. In vitro, PCN directly inhibited hepatic stellate cell transdifferentiation to a profibrogenic phenotype, although the cells did not express the PXR (in contrast with hepatocytes), suggesting that PCN acts independently of the PXR. Mice with a functionally disrupted PXR gene (PXR\u2212\/\u2212) did not respond to the antifibrogenic effects of PCN, in contrast with wild-type (PXR+\/+) mice, demonstrating an antifibrogenic role for the PXR in vivo. However, PCN inhibited the transdifferentiation of PXR\u2212\/\u2212-derived mouse hepatic stellate cells in vitro, confirming that there is also a PXR-independent antifibrogenic effect of PCN through a direct interaction with hepatic stellate cells. These data suggest that the PXR is antifibrogenic in rodents in vivo and that a PXR-independent target for PXR activators exists in hepatic stellate cells that also functions to inhibit fibrosis.<\/jats:p>","DOI":"10.1042\/bj20041598","type":"journal-article","created":{"date-parts":[[2005,4,27]],"date-time":"2005-04-27T08:32:50Z","timestamp":1114590770000},"page":"601-608","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Pregnenolone-16\u03b1-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms"],"prefix":"10.1042","volume":"387","author":[{"given":"Carylyn\u00a0J.","family":"MAREK","sequence":"first","affiliation":[{"name":"School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven\u00a0J.","family":"TUCKER","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios\u00a0K.","family":"KONSTANTINOU","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy\u00a0J.","family":"ELRICK","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dee","family":"HAEFNER","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalambos","family":"SIGALAS","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme\u00a0I.","family":"MURRAY","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Aberdeen, Medical School Buildings, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"GOODWIN","sequence":"additional","affiliation":[{"name":"Nuclear Receptor Discovery Research, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew\u00a0C.","family":"WRIGHT","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2005,4,26]]},"reference":[{"key":"2021112214593995400_B1","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1074\/jbc.275.4.2247","article-title":"Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury","volume":"275","author":"Friedman","year":"2000","journal-title":"J. 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