Studies of gene expression and physiological roles of cellular retinol-binding protein, type II in the small intestine.

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We have reported that the gene expression of cellular retinol-binding protein, type II (CRBPII), which plays important roles in vitamin A uptake, transport and their metabolisms in small intestinal cells, is transcriptionally regulated by dietary fatty acids. In the present study, we further investigated the mechanism of transcriptional regulation of CRBPII gene and the effects on the intestinal vitamin A uptake and metabolisms modulated by fatty acids in the small intestine. We demonstrated in the cotransfection assay that the heterodimer of peroxisome proliferator-activated receptor α (PPARα) and retinoid X receptor (RXR) induced the rat CRBPII gene promoter's transactivity by binding to two putative nuclear receptor response elements (RXRE and RE3) in the presence of PPAR ligands such as linoleic acid and arachidonic acid. In the rat small intestine, not only PPARα but also PPARδ trasncripts was abundantly expressed. Therefore, in the next step, we examined the differences of ligand responsiveness between PPARα and PPARδ in the human small intestine-like cell lines Caco-2. In the one-hybrid assay, broad and great ligand responsiveness was seen in PPARα-mediated transactivity compared to PPARδ. Moreover, PPARα but not PPARδ preferentially interacted with coactivator p300, which was abundantly expressed in the rat small intestine. We further revealed that the increase of small intestinal CRBPII gene expression level by fatty acids led to an increase in the cellular uptake and metabolisms of vitamin A in the small intestine. These results suggest that the expressions of PPAR-dependent genes in the small intestine including CRBPII may be coordinately regulated by PPARα and PPARδ.