Vitamin D Prevents the Intestinal Fibrosis Via Induction of Vitamin D Receptor and Inhibition of Transforming Growth Factor-Beta1/Smad3 Pathway

Background and Aims Vitamin D deficiency in patients with inflammatory bowel disease (IBD) is associated with greater disease activity and lower quality of life. Intestinal fibrosis is a main complication of IBD. However, the effect of vitamin D on intestinal fibrosis remains unclear. We investigated the prophylactic effect and the underlying mechanism of vitamin D on the intestinal fibrosis in vitamin D-deficient mice with chronic colitis. Methods Vitamin D-deficient mice were randomized into two groups receiving the vitamin D-deficient or vitamin D-sufficient diet from weaning (week 4). Intestinal fibrosis was induced by six-weekly 2,4,6-trinitrobenzene sulfonic acid administrations from week 8. At week 14, the productions of extracellular matrix (ECM) and total collagen were measured in the colons, and TGF-beta 1/Smad3 signal transduction was examined in isolated colonic subepithelial myofibroblasts (SEMF). The expression of vitamin Dreceptor (VDR), alpha-SMA and Collagen I in normal SEMF and VDR-null SEMF exposed to TGF-beta 1 and/or 1,25(OH)(2)D-3 was measured. Results Vitamin D significantly reduced the histological scoring, ECM and collagen productions in the colons and decreased the levels of TGF-beta 1, Smad-3, p-Smad3 and Collagen I in SEMF. 1,25(OH)(2)D-3-induced VDR expression and decreased TGF-beta 1-stimulated a-SMA and Collagen I expressions in SEMF. Knocking down VDR expression in SEMF abolished the effect of 1,25(OH)(2)D-3. Conclusions Vitamin D has prophylactic effect on intestinal fibrosis in the vitamin D-deficient mice with chronic colitis, which may be associated with the inhibited activation of TGF-b1/Smad3 pathway in the SEMF via VDR induction.