All-trans retinoic acid enhances differentiation and influences permeability of intestinal Caco-2 cells under serum-free conditions.
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.
Baltes
Steffen
S
Institute for Food Toxicology, University of Veterinary Medicine Hannover, Foundation Bischofsholer Damm 15, 30173 Hannover, Germany.
Nau
Heinz
H
Lampen
Alfonso
A
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D016895:Culture Media, Serum-Free; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology*; D014801:Vitamin A / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D012333:RNA, Messenger; D014801:Vitamin A; D014212:Tretinoin; D000469:Alkaline Phosphatase