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Reversal of liver fibrosis in aryl hydrocarbon receptor null mice by dietary vitamin A depletion

Andreola, Fausto and Calvisi, Diego Francesco and Elizondo, Guillermo and Jakowlew, Sonia B. and Mariano, Jennifer and Gonzalez, Frank J. and De Luca, Luigi M. (2004) Reversal of liver fibrosis in aryl hydrocarbon receptor null mice by dietary vitamin A depletion. Hepatology, Vol. 39 (1), p. 157-166. eISSN 1527-3350. Article.

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DOI: 10.1002/hep.20004


Aryl hydrocarbon receptor (AHR)-null 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 β(TGF β) 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-null 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 β1, TGFβ2, and TGFβ3 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 TGFβ receptors, TGFβRI and TGFβRII, 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 γ(PPARγ) 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 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.

Item Type:Article
ID Code:1244
Uncontrolled Keywords:Aryl hydrocarbon receptor (AHR), liver fibrosis phenotype, liver retinoid concentration, growth factorβ(TGFβ), proliferator-activated receptorγ (PPARγ)
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Copyright Holders:© 2004 by the American Association for the Study of Liver Diseases
Deposited On:18 Aug 2009 10:04

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