{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T19:25:55Z","timestamp":1769282755107,"version":"3.49.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4261,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Aryl hydrocarbon receptor (AHR)-<jats:italic toggle=\"yes\">null<\/jats:italic> mice display a liver fibrosis phenotype that is associated with a concomitant increase in liver retinoid concentration, tissue transglutaminase type II (TGaseII) activity, transforming growth factor\u03b2 (TGF\u03b2) overexpression, and accumulation of collagen. To test the hypothesis that this phenotype might be triggered by the observed increase in liver retinoid content, we induced the condition of retinoid depletion by feeding AHR-<jats:italic toggle=\"yes\">null<\/jats:italic> mice a vitamin A- deficient diet with the purpose to reverse the phenotype. Liver retinoid content decreased sharply within the first few weeks on the retinoid-deficient diet. Analysis of TGF\u03b21, TGF\u03b22, and TGF\u03b23 expression revealed a reduction to control levels in the AHR -\/- mice accompanied by parallel changes in TGaseII protein levels. In addition, we observed an increase in the TGF\u03b2 receptors, TGF\u03b2 RI and TGF\u03b2 RII, as well as in Smad4, and their reduction to wild-type mouse liver levels in AHR -\/- mice fed the retinoid-deficient diet. Reduction of peroxisomal proliferator-activated receptor \u03b3 (PPAR\u03b3) messenger RNA (mRNA) and protein levels in AHR -\/- mice was consistent with the presence of hepatic stellate cell (HSC) activation and liver fibrosis. Vitamin A deficiency normalized PPAR\u03b3 expression in AHR -\/- mice. In conclusion, livers from AHR -\/- mice fed the vitamin A-deficient diet showed a decrease in collagen deposition, consistent with the absence of liver fibrosis. 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