Journal of Lipid Research
Volume 44, Issue 2, February 2003, Pages 280-295
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Research Article
PPARβ regulates vitamin A metabolism-related gene expression in hepatic stellate cells undergoing activation

https://doi.org/10.1194/jlr.M200376-JLR200Get rights and content
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Activation of cultured hepatic stellate cells correlated with an enhanced expression of proteins involved in uptake and storage of fatty acids (FA translocase CD36, Acyl-CoA synthetase 2) and retinol (cellular retinol binding protein type I, CRBP-I; lecithin:retinol acyltransferases, LRAT). The increased expression of CRBP-I and LRAT during hepatic stellate cells activation, both involved in retinol esterification, was in contrast with the simultaneous depletion of their typical lipid-vitamin A (vitA) reserves. Since hepatic stellate cells express high levels of peroxisome proliferator activated receptor β (PPARβ), which become further induced during transition into the activated phenotype, we investigated the potential role of PPARβ in the regulation of these changes. Administration of L165041, a PPARβ-specific agonist, further induced the expression of CD36, B-FABP, CRBP-I, and LRAT, whereas their expression was inhibited by antisense PPARβ mRNA. PPARβ-RXR dimers bound to CRBP-I promoter sequences.

Our observations suggest that PPARβ regulates the expression of these genes, and thus could play an important role in vitA storage. In vivo, we observed a striking association between the enhanced expression of PPARβ and CRBP-I in activated myofibroblast-like hepatic stellate cells and the manifestation of vitA autofluorescent droplets in the fibrotic septa after injury with CCl4 or CCl4 in combination with retinol.

liver fibrosis
peroxisome proliferator-activated receptor β
fatty acid binding protein
CD36
ACS2
cellular retinol binding protein
lecithin:retinol acyltransferases

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    Abbreviations

    ACS

    acyl-CoA synthetase

    ARAT

    acyl-CoA:retinol acyltransferase

    FAT/CD36

    FA translocase

    CRABP

    cellular retinoic acid binding protein

    CRBP

    cellular retinol binding protein

    FABP

    fatty acid binding protein

    LCFA

    long chain fatty acid

    LRAT

    lecithin:retinol acyltransferase

    PPAR

    peroxisome proliferator-activated receptor

    PPRE

    PPAR-responsive element

    RAR

    retinoic acid receptor

    RARE

    RAR-responsive element

    RBP

    retinol-binding protein

    RE

    retinyl ester

    RXR

    retinoid X receptor

    vitA

    vitamin A