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A more recent version of this article appeared on February 1, 2003

Papers In Press, published online ahead of print November 16, 2002
J. Lipid Res., doi:10.1194/jlr.M200376-JLR200
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Submitted on September 20, 2002
Revised on November 13, 2002
Accepted on November 14, 2002

PPARbeta regulates vitamin A-metabolism related gene expression in hepatic stellate cells undergoing activation

K. Hellemans, K. Rombouts, E. Quartier, A. S. Dittié, A. Knorr, L. Michalik, V. Rogiers, F. Schuit, W. Wahli, and A. Geerts

Laboratory of Molecular Liver Cell Biology, Free University Brussels, Brussel 1090

Corresponding Author: khellem{at}minf.vub.ac.be

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 HSC activation, both involved in retinol esterification, was in contrast with the simultaneous depletion of their typical lipid/vitamin A reserves. Since HSC express high levels of peroxisome proliferator activated receptor beta (PPARbeta ), which become further induced during transition into the activated phenotype, we investigated the potential role of PPARbeta in the regulation of these changes. Administration of L165041, a PPARbeta -specific agonist, further induced the expression of CD36, B-FABP, CRBP-I and LRAT, whereas their expression was inhibited by antisense PPARbeta mRNA. PPARbeta :RXR dimers bound to CRBP-I promoter sequences. Our observations suggest that PPARbeta regulates the expression of these genes, and thus could play an important role in vitamin A storage. In vivo, we observed a striking association between the enhanced expression of PPARbeta and CRBP-I in activated myofibroblast like-HSC and the manifestation of vitamin A autofluorescent droplets in the fibrotic septa after injury with CCl4 or CCl4 in combination with retinol.


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