J Pharmacol Sci. 2019 Jul 26. pii: S1347-8613(19)35687-7. doi: 10.1016/j.jphs.2019.06.012. [Epub ahead of print]

Retinoic acid promotes barrier functions in human iPSC-derived intestinal epithelial monolayers.

Yamada S¹, Kanda Y².

Abstract

Vitamin A (VA) is a fat-soluble micronutrient that plays essential roles in various biological processes, including cell growth, differentiation, and apoptosis. In the intestine, VA are known to promote mucosal homeostasis and immunity. However, the effect of VA in intestinal development has not been well elucidated. In the present study, we generated human intestine organoids from human induced pluripotent stem cells (iPSCs), and investigated the effect of the VA active metabolite all-trans retinoic acid (RA), on differentiation into intestinal organoids. As a result, RA increased the gene expression of a drug-metabolizing enzyme CYP3A4, as a functional molecule of intestinal mature development, in iPSC-derived intestinal organoids. In addition, RA increased transepithelial electrical resistance, an indicator of epithelial integrity, and decreased the permeability of monolayers to fluorescein isothiocyanate-labeled dextran in intestinal epithelial monolayers. Finally, RA increased the expression of ZO-1, a marker of tight junctions, which are essential for intestinal epithelial barrier function. Taken together, these results indicate that RA promotes barrier functions of iPSC-derived intestinal epithelial monolayers by increasing ZO-1 expression.

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