UC San Diego
Vitamin D regulates MUC17 expression in Caco-2 cells
- Author(s): Tabikh, Sara Quraish
- et al.
Mucins are essential components of the gastrointestinal (GI) barrier and their downregulation contributes to the pathogenesis of chronic GI inflammation. Calcium plays an important role in stabilizing negatively charged mucins expressed by intestinal cells. Vitamin D regulates ion homeostasis and intestinal calcium absorption, through the nuclear vitamin D receptor (VDR). MUC17 gene regulator contains a VDR responsive element. We hypothesized that lack of VDR expression would disrupt mucin expression in intestinal epithelial cells. Methods : Caco-2 cells treated with siVDR or untreated control were tested for MUC17 mRNA expression by PCR and for MUC17 levels by immunohistochemistry. Treatment with low calcium concentration by calcium switch and vitamin D3 was also studied. Results: siVDR Caco-2 cells showed significant lower levels of immunohistochemically localizable MUC17 than the Caco-2 controls (p<0.01). MUC17 mRNA expression was also diminished by a factor of 2.5 in siVDR cells. When cells were exposed to low calcium, little MUC17 was detectable and thus the effect of gene silencing was intensified. Restoration of calcium levels in the siVDR Caco-2 evoked a rapid short-lived recovery of MUC17 mRNA expression. Vitamin D3 treatment had no effect on both MUC17 mRNA and protein in siVDR Caco-2 cells. However, untreated controls expressing normal levels of VDR showed an increased MUC17 mRNA and protein expression after D3 treatment. Our data underline the importance of calcium homeostasis in the intestinal epithelium and show that vitamin D promotes mucin expression and homeostasis