Increased vitamin D receptor level enhances 1,25-dihydroxyvitamin D3-mediated gene expression and calcium transport in Caco-2 cells

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
A ShaoJames C Fleet

Abstract

Altered vitamin D receptor (VDR) level has been proposed to explain differences in intestinal responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We tested whether the enterocyte VDR level influences 1,25(OH)2D3-mediated gene expression and transepithelial calcium (Ca) transport in the human intestinal cell line Caco-2. Cells were stably transfected with a human metallothionein (hMT) IIA promoter-human VDR (hVDR) complementary DNA (cDNA) transgene that overexpressed hVDR in response to heavy metals. In MTVDR clones, induction of 25-hyroxyvitamin D3-24-hydroxylase (24-OHase) messenger RNA (mRNA) expression by 1,25(OH)2D3 (10(-9) M, 4 h) was correlated to metal-induced changes in nuclear VDR level (r2 = 0.99). In MTVDR clones, basal VDR level was 2-fold greater and 1,25(OH)2D3-mediated Ca transport (10(-7) M, 24 h) was 43% higher than in parental Caco-2 cells. Treatment of MTVDR clones with Cd (1 microM, 28 h) increased VDR level by 68%, significantly enhanced 1,25(OH)2D3-mediated Ca transport by 24%, and increased accumulation of calbindin D9K mRNA by 76% relative to 1,25(OH)2D3 alone. These observations support the hypothesis that the enterocyte VDR level is an important modulator of intestinal responsiveness to 1,25(OH)2D3.

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Citations

Jul 28, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Perla C Reyes-Fernandez, James C Fleet
Apr 13, 2017·Molecular and Cellular Endocrinology·James C Fleet
Dec 25, 2004·Physiological Reviews·Joost G J HoenderopRené J M Bindels
Aug 21, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Rebecca A ReplogleJames C Fleet
Aug 16, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·James C FleetRichard J Wood
Dec 25, 2010·Critical Reviews in Clinical Laboratory Sciences·James C Fleet, Ryan D Schoch
Oct 17, 2017·Immunology·Majid Pahlevan KakhkiMehrdad Behmanesh
Jan 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yi YinShuyuan Yeh
Jun 20, 2003·Joint, Bone, Spine : Revue Du Rhumatisme·Pawel Szulc, Pierre Jean Meunier

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