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INFLAMMATION/IMMUNITY/MEDIATORS
Departments of 1Nutrition and 4Biochemistry, CHU Sainte-Justine, Université de Montréal, Montreal; 2Group on the Intestinal Epithelium, Canadian Institute of Health Research and Department of Cellular Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke; and 3Research Institute, McGill University, Montreal, Quebec, Canada
Submitted 28 June 2007 ; accepted in final form 2 October 2007
Dietary vitamin A and its active metabolites are essential nutrients for many functions as well as potent regulators of gene transcription and growth. Although the epithelium of the small intestine is characterized by rapid and constant renewal and enterocytes play a central role in the absorption and metabolism of alimentary retinol, very little is known about the function of retinoids in the human gastrointestinal epithelium and mechanisms by which programs engage the cell cycle are poorly understood. We have assessed the effects of 10 µM 9- and 13-cis-retinoic acid (RA) on proliferation and differentiation processes, lipid esterification, apolipoprotein (apo) biogenesis and lipoprotein secretion along with nuclear factor gene transcription. Treatment of Caco-2 cells with RA at different concentrations and incubation periods revealed the reduction of thymidine incorporation in 60% preconfluent or 100% confluent cells. Concomitantly, RA 1) modulated D-type cyclins by reducing the mitogen-sensitive cyclin D1 and upregulating cyclin D3 expressions and 2) caused a trend of increase in p38 MAPK, which triggers CDX2, a central protein in cell differentiation. RA remained without effect on lipoprotein output and apo synthesis, even for apo A-I that possesses RARE in its promoter. RA, in combination with 22-hydroxycholesterol, could induce apo A-I gene expression without any impact on apo A-I mass. Only the gene expression of peroxisome proliferator-activated receptor (PPAR)β, retinoic receptor (RAR)β, and RAR
was augmented and no alteration was noted in PPAR
, PPAR
, liver X receptor (LXR)
, LXRβ, and retinoid X receptors. Taken together, these data highlight RA-induced cell differentiation via specific signaling without a significant impact on apo A-I synthesis.
retinoids; apolipoproteins; lipoproteins; nuclear factors; lipids
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