Dietary supplementation with vitamin D stimulates intestinal epithelial cell turnover after massive small bowel resection in rats

Abstract

While the endocrine action of the active metabolite 1,25-dihydroxyvitamin D (VtD) has been well characterized in relation to the maintenance of plasma calcium and phosphate homeostasis through regulation of intestinal absorption, recent research has focused on its autocrine and/or paracrine activities. Such activities have been best characterized in intestine, where VtD regulates cell differentiation and maturation. The purpose of this study was to evaluate the effect of VtD on enterocyte turnover in a rat model of short bowel syndrome (SBS). Male rats were divided into four groups: sham rats underwent bowel transection, sham-VtD rats underwent bowel transection and were treated oral VtD, SBS rats underwent a 75% bowel resection, and SBS-VtD rats underwent bowel resection and were treated with VtD. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at sacrifice. Illumina's digital gene expression (DGE) analysis was used to determine VtD pathway-related gene expression profiling. VtD receptor (VDR) and its promoter, Bax and Bcl-2 mRNA expression were determined using real-time PCR. Western blotting was used to determine p-ERK, Bax and β-catenin protein levels. From the total of 20,000 probes, 11 genes related to VtD signaling were investigated. Of these genes, five were found to be up-regulated in SBS versus sham animals with a relative change in gene expression level of 20%, five remained unchanged, and one was down-regulated. VtD treatment in sham and SBS rats resulted in significant up-regulation of the VDR gene and its promoter's expression. SBS-VtD rats demonstrated a significant increase in all intestinal mucosal parameters compared to SBS animals. A significant increase in cell proliferation in SBS-VtD rats was accompanied by increased β-catenin protein levels. A significant decrease in cell apoptosis in this group was correlated with lower Bax/Bcl-2 mRNA and protein levels. In a rat model of SBS, dietary supplementation with VtD stimulates enterocyte turnover, which correlates with up-regulated VtD receptor expression in the remaining small intestine.