Vitamin A (VA) is a fat-soluble nutrient that plays essential biological processes, such as cell growth, differentiation and apoptosis and has been thought to be a regulator of mucosal homeostasis and immunity in intestinal development. However, the potential action of VA in intestinal differentiation has not yet been precisely elucidated.
In the present study, we used human induced pluripotent stem cells (iPSCs) as a model of human fetal stage, and investigated the effect of VA derivatives, such as all-trans retinoic acid (RA), on the differentiation into intestinal organoids. RA increased the gene expression of drug-metabolizing enzymes, such as CYP3A4, in iPSC-derived intestinal organoids. RA also increased the transepithelial electrical resistance, an indicator of epithelial integrity, and decreased the permeability of FITC-dextran in the monolayers. Since the intestinal epithelial barrier is formed through tight junction, we further examined the expression level of ZO-1, which is a well-known marker of tight junction. We found that RA increased ZO-1 level in the intestinal epithelial monolayers.
Taken together, these results indicate that RA promotes barrier functions of iPSC-derived intestinal epithelial monolayers by increasing the level of ZO-1.