RETINOIC ACID INCREASES CELLULAR RETINOL-BINDING PROTEIN-II MESSENGER-RNA AND RETINOL UPTAKE IN THE HUMAN INTESTINAL CACO-2 CELL-LINE

Cellular retinol binding protein II (CRBPII) is an abundant small inte stinal protein that facilitates vitamin A trafficking and metabolism. The magnitude of retinol uptake and metabolism correlate to CRBPII lev els in the human intestinal Caco-2 cell line. To investigate the impor tance of retinoic acid receptor response elements in the promoter of t he CRBPII gene, retinoic acid regulation of CRBPII expression and vita min A absorption was studied in differentiated Caco-2 cells. All-trans - or 9-cis-retinoic acid increased CRBPII mRNA levels two- to threefol d. This was associated with a 50% increase in retinol absorption. Reti noic acid receptor beta and apolipoprotein A1 regulatory protein-1, tw o nuclear receptors that bind to the CRBPII promoter, were also induce d, whereas other retinoid and orphan receptors were not. Thus, retinoi c acid may regulate CRBPII expression directly or by selectively chang ing levels of nuclear receptors or other factors. These studies are th e first to demonstrate that retinoic acid can modulate endogenous CRBP II mRNA levels and retinol absorption in Caco-2 cells and suggest that human intestinal vitamin A absorption may be regulated by retinoids.