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

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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).

Conflict of interest

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Authors and Affiliations

  1. Department of General Surgery, Affiliated Zhongda Hospital, Southeast University Medical School, 87 Ding Jia Qiao Road, Nanjing, 210089, Jiangsu, China

    Qingsong Tao, Baochai Wang, Xiaohua Jiang & Zheng Pan

  2. Department of Surgery, Haian People’s Hospital, Nantong University Medical School, Nantong, 226600, Jiangsu, China

    Yu Zheng

  3. Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, 210093, Jiangsu, China

    Jianan Ren

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  1. Qingsong Tao
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Correspondence to Qingsong Tao.

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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

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