Abstract
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-β1/Smad3 signal transduction was examined in isolated colonic subepithelial myofibroblasts (SEMF). The expression of vitamin D receptor (VDR), α-SMA and Collagen I in normal SEMF and VDR-null SEMF exposed to TGF-β1 and/or 1,25(OH)2D3 was measured.
Results
Vitamin D significantly reduced the histological scoring, ECM and collagen productions in the colons and decreased the levels of TGF-β1, Smad-3, p-Smad3 and Collagen I in SEMF. 1,25(OH)2D3-induced VDR expression and decreased TGF-β1-stimulated α-SMA and Collagen I expressions in SEMF. Knocking down VDR expression in SEMF abolished the effect of 1,25(OH)2D3.
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-β1/Smad3 pathway in the SEMF via VDR induction.
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Abbreviations
- IBD:
-
Inflammatory bowel disease
- CD:
-
Crohn’s disease
- SEMF:
-
Subepithelial myofibroblasts
- VDR:
-
Vitamin D receptor
- ECM:
-
Extracellular matrix
- α-SMA:
-
α-Smooth muscle actin
- p-Smad3:
-
Smad3 phosphorylation
- Vit D:
-
Vitamin D
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Acknowledgments
This study was supported by grants from National Foundation for Natural Scientific Research of China (No 81000153) and Foundation for Natural Scientific Research of Jiangsu Province (BK2010415).
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Tao, Q., Wang, B., Zheng, Y. et al. Vitamin D Prevents the Intestinal Fibrosis Via Induction of Vitamin D Receptor and Inhibition of Transforming Growth Factor-Beta1/Smad3 Pathway. Dig Dis Sci 60, 868–875 (2015). https://doi.org/10.1007/s10620-014-3398-6
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DOI: https://doi.org/10.1007/s10620-014-3398-6