Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor gamma and hepatocyte nuclear factor 4alpha.

Excessive cellular cholesterol is transported to the liver by a pathway called 'reverse cholesterol transport.' Scavenger receptor class B, type I (SR-BI) mediates cholesterol uptake in the liver. Polyunsaturated fatty acids, known to activate peroxisome proliferator-activated receptor (PPAR), have been reported to increase hepatic cholesterol uptake. We found in the present study that PPARgamma induces expression of SR-BI in rat hepatocytes, liver endothelial cells, and Kupffer cells. In contrast, PPARalpha increased SR-BI levels only in hepatocytes and liver endothelial cells. PPARgamma/RXR binds to a response element between -459 and -472 bp in the human SR-BI promoter. Furthermore, hepatocyte nuclear factor 4alpha (HNF4alpha) was found to enhance PPARgamma-mediated SR-BI transcription. Thiazolidinedione (TZD)-activated PPARgamma/RXR increased hepatic SR-BI levels, which may lead to increased hepatic cholesterol uptake and less accumulation of lipids in peripheral tissues. The present results are in agreement with previous reports, indicating that specific PPARgamma-agonists (such as TZDs) protect against atherosclerosis.
Mesh Terms:
Animals, Antigens, CD36, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Binding Sites, COS Cells, DNA Mutational Analysis, DNA-Binding Proteins, Hepatocyte Nuclear Factor 4, Hepatocytes, Humans, Kinetics, Kupffer Cells, Liver, Membrane Proteins, Mice, Phosphoproteins, Promoter Regions, Genetic, Receptors, Cytoplasmic and Nuclear, Receptors, Immunologic, Receptors, Lipoprotein, Receptors, Retinoic Acid, Receptors, Scavenger, Response Elements, Retinoid X Receptors, Scavenger Receptors, Class B, Thiazoles, Thiazolidinediones, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured
Biochem. Biophys. Res. Commun. Jun. 06, 2003; 305(3);557-65 [PUBMED:12763030]
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