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Hepatic fibrosis in mice lacking liver vitamin A stores
Author(s) -
Jiang Hongfeng,
Piantedosi Roseann,
Blaner William S.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.730.4
Subject(s) - hepatic stellate cell , hepatic fibrosis , endocrinology , medicine , retinol , fibrosis , chemistry , vitamin , lipid droplet , timp1 , hydroxyproline , downregulation and upregulation , biology , biochemistry , gene expression , gene
Loss of retinyl esters and lipid droplets from hepatic stellate cells (HSCs) is one of the first events in the development of hepatic fibrosis. Since lecithin:retinol acyltransferase‐deficient ( Lrat −/− ) mice lack HSC retinyl esters and lipid droplets, we investigated how this absence influences development of CCl 4 ‐induced hepatic fibrosis. We also induced fibrosis in mice lacking diacylglycerol acyltransferase 1 ( Dgat1 −/− ), an enzyme that can synthesize retinyl esters. Hepatic retinol and retinyl ester contents of CCl 4 ‐treated wild type and Dgat1 −/− mice were significantly lower than sham‐treated mice. Trichrome staining and qRT‐PCR indicated that, although liver collagen content increased in all the CCl 4 ‐treated groups, more collagen was present in livers of Lrat −/− and Dgat1 −/− mice compared to wild type. We measured mRNA levels by qRT‐PCR of a number of factors implicated in fibrosis development. TGFβ mRNA levels were similarly elevated in all CCl 4 ‐treated groups but levels for Timp1, Cyp2S1 and Cyp26A1 were significantly more upregulated in Lrat −/− and Dgat1 −/− mice than in wild type mice. Our data suggest that the absence of HSC vitamin A stores can influence the progression of hepatic fibrosis.