Abstract
Simple SummaryThe gastric epithelium comprises multiple cell types that undergo continuous renewal through controlled proliferation, differentiation and death. Several vitamins, such as vitamin D (VD), are known to contribute to tissue homeostasis and numerous studies have shown the importance of VD in different body organ systems. However, VD’s normal function in the stomach is understudied. To better understand the role of VD in the murine stomach, we initially confirmed the expression of VD receptors (VDR) in the stomach. Mice were fed a VD-deficient diet for 3 months. The results showed that the proton pump of acid-secreting parietal cells was downregulated in vitamin D-deficient mice and contributed to an abnormal gastric physiology. Moreover, this diet increased the gastrin hormone gene expression and increased gastric epithelial cell proliferation. These findings suggest essential biological roles for VDR and VD in gastric epithelial homeostasis. Future research will be required to explore this phenomenon in humans.Unlike other organs, the importance of VD in a normal stomach is unknown. This study focuses on understanding the physiological role of vitamin D in gastric epithelial homeostasis. C57BL/6J mice were divided into three groups that were either fed a standard diet and kept in normal light/dark cycles (SDL), fed a standard diet but kept in the dark (SDD) or fed a vitamin D-deficient diet and kept in the dark (VDD). After 3 months, sera were collected to measure vitamin D levels by LC-MS/MS, gastric tissues were collected for immunohistochemical and gene expression analyses and gastric contents were collected to measure acid levels. The VDD group showed a significant decrease in the acid-secreting parietal cell-specific genes Atp4a and Atp4b when compared with the controls. This reduction was associated with an increased expression of an antral gastrin hormone. VDD gastric tissues also showed a high proliferation rate compared with SDL and SDD using an anti-BrdU antibody. This study indicates the requirement for normal vitamin D levels for proper parietal cell functions.
Highlights
Vitamins are nutritional factors required in small quantities that play important roles in human development, reproduction and tissue maintenance [1]
We observed the binding of VD receptor (VDR) antibodies along the forestomach and epithelial lining of the corpus (Figure 1c,d)
We found that within the gastric mucosa of VDD mice, the relative mRNA expression of these genes was moderately downregulated when compared with the SDL control mice group (Figure 8a–c)
Summary
Vitamins are nutritional factors required in small quantities that play important roles in human development, reproduction and tissue maintenance [1]. 7-dehydrocholesterol, the precursor of VD3, is naturally found in epidermal cells. The enzymes sterol 27-hydroxylase (CYP27A1) and 25-hydroxylase (CYP2R1) turn VD3 into 25-hydroxyvitamin D3 (25OHD3), which is primarily translocated to the kidney via the DBP where it is hydroxylated further by 1α-hydroxylase (CYP27B1) to become the biologically active form, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). This active form is transported to multiple target tissues, including bone and the intestines, to perform its biological functions [5]
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