The effect of differentiation on 1,25 dihydroxyvitamin D-mediated gene expression in the enterocyte-like cell line, Caco-2.

Journal of Cellular Physiology
Min CuiJ C Fleet

Abstract

We examined 1,25 dihydroxyvitamin D (1,25(OH)(2)D(3))-induced expression of 25-hydroxyvitamin D(3) 24-hydroxylase (CYP24) and apical calcium channel (TRPV6) mRNA levels in 2-, 9-, and 15-day cultures Caco-2 cells that model proliferating, post-proliferative, and differentiated enterocytes. 1,25(OH)(2)D(3)-induced (10 nM, 8 h) CYP24 and TRPV6 mRNA levels were significantly greater in differentiated and post-proliferative than proliferating Caco-2 cells (>16X and >3X, respectively). Neither CYP24 mRNA half-life nor induction of a -298 bp rat CYP24 promoter-luciferase reporter construct (10 nM 1,25(OH)(2)D(3), 24 h) were different between proliferating and post-proliferating Caco-2 cells. We next tested whether the blunted response of natural genes to 1,25(OH)(2)D(3) in proliferating Caco-2 cells is due to altered chromatin remodeling. VDR and coactivator protein levels do not increase with differentiation but the level of the co-repressor Alien falls by 50% with differentiation. Over-expression of Alien reduced 1,25(OH)(2)D(3)-induced activity of a minimal VDRE containing promoter-luciferase construct by more than 60% in differentiated Caco-2 cells while siRNA knockdown of Alien in proliferating Caco-2 cells increased 1,25(OH)(2)...Continue Reading

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Citations

Jan 14, 2011·Journal of Nutritional Science and Vitaminology·Jun InoueRyuichiro Sato
Aug 5, 2009·Critical Reviews in Clinical Laboratory Sciences·Elzbieta Gocek, George P Studzinski
Sep 12, 2012·Cancer Investigation·Gabriela PicottoNori Tolosa de Talamoni
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Jun 19, 2012·Ageing Research Reviews·Verónica Gonzalez Pardo, Ana Russo de Boland
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May 27, 2014·Frontiers in Physiology·Moray J Campbell
Feb 20, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Geneviève MorinGeneviève Mailhot

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