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

• Main Authors: Karine Hellemans, Krista Rombouts, Erik Quartier, Andrea S. Dittié, Andreas Knorr, Liliane Michalik, Vera Rogiers, Frans Schuit, Walter Wahli, Andrea Geerts
• Format: Article
• Language: English
• Published: Elsevier 2003-02-01
• Series: Journal of Lipid Research
• Subjects: liver fibrosis; peroxisome proliferator-activated receptor β; fatty acid binding protein; CD36; ACS2; cellular retinol binding protein
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520312153

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.