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All-trans retinoic acid enhances differentiation and influences permeability of intestinal Caco-2 cells under serum-free conditions.

Baltes S, Nau H, Lampen A

Institute for Food Toxicology, University of Veterinary Medicine Hannover, Foundation Bischofsholer Damm 15, 30173 Hannover, Germany.

Vitamin A and retinoids are essential nutrients for the differentiation of epithelia. Vitamin A deficiency is accompanied by an impairment in intestinal integrity. We investigated whether retinoids influence the differentiation and permeability of Caco-2 cells under serum-free culture conditions as a model for the intestinal epithelium. Treatment of the Caco-2 cells with retinoic acids (RA) resulted in an increased specific activity, enhanced mRNA expression, and induction of the 5'-flanking promoter activity of the marker enzyme for the differentiation intestinal alkaline phosphatase. Surprisingly, permeability of the Caco-2 monolayer, as measured by transepithelial electric resistance and [3H]-mannitol flux, was found to be enhanced by RA. Treatment with RA had only a slight effect on the mRNA expression of the tight junction-associated proteins occludin, ZO-1, claudin-1, -3, and -4, but enhanced the expression of claudin-2, which was recently suggested to form a paracellular ion channel. The role of retinoids as potent inducers of epithelial differentiation was confirmed for the Caco-2 cells under serum-free culture conditions and it was concluded that IAP is a target gene of RA. The inverse regulation of the permeability by RA under these serum-free conditions showed that other mechanisms, which are essential to regulate intestinal epithelial integrity with respect to decreased permeability, have to be identified.

Published 21 December 2004 in Dev Growth Differ, 46(6): 503-14.
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