The gene encoding the human ileal bile acid-binding protein ( I-BABP) is regulated by peroxisome proliferator-activated receptors.
Peroxisome proliferator-activator receptors ( PPAR) are involved in cholesterol homeostasis through the regulation of bile acids synthesis, composition, and reclamation. As ileal bile acid-binding protein ( I-BABP) is thought to play a crucial role in the enterohepatic circulation of bile acids, we investigated whether I-BABP gene expression could also be affected by PPAR. Indeed, treatment with the PPARalpha- PPARbeta/delta agonist bezafibrate led to the up-regulation of I-BABP mRNA levels in the human intestine-derived Caco-2 cells. Cotransfections of the reporter-linked human I-BABP promoter (hI-BABP-2769/+44) together with PPAR and RXR expression vectors demonstrated that the fibrate- mediated induction of the I-BABP gene is dependent on PPARalpha or PPARbeta/delta. Using progressive 5' deletions of the hI-BABP promoter and sequence analysis, we identified a putative PPAR-binding site located at the position -198 and -186 upstream of the transcription initiation site. Electrophoretic mobility shift assays showed that the PPAR/RXR heterodimer can specifically bind to this PPRE-like motif. The deletion of the PPRE within the hI-BABP promoter abolished the PPAR-mediated transactivation in transient transfection assays. The regulation of the I-BABP promoter by PPAR appears species-specific, as the mouse I-BABP promoter, which lacks a conserved PPRE, was not responsive to exogenous PPAR expression in the presence of bezafibrate. Our findings show that the I-BABP gene may be a novel target for PPAR in humans and further emphasize the role for PPAR in the control of bile acid homeostasis.[1]References
- The gene encoding the human ileal bile acid-binding protein (I-BABP) is regulated by peroxisome proliferator-activated receptors. Landrier, J.F., Thomas, C., Grober, J., Zaghini, I., Petit, V., Poirier, H., Niot, I., Besnard, P. Biochim. Biophys. Acta (2005) [Pubmed]
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