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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  • 作者:Qingsong Tao ; Baochai Wang ; Yu Zheng ; Xiaohua Jiang…
  • 关键词:Vitamin D ; Intestinal fibrosis ; Myofibroblast ; TGF ; β1 ; Smad3 ; VDR
  • 刊名:Digestive Diseases and Sciences
  • 出版年:2015
  • 出版时间:April 2015
  • 年:2015
  • 卷:60
  • 期:4
  • 页码:868-875
  • 全文大小:6,955 KB
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  • 作者单位:Qingsong Tao (1)
    Baochai Wang (1)
    Yu Zheng (2)
    Xiaohua Jiang (1)
    Zheng Pan (1)
    Jianan Ren (3)

    1. Department of General Surgery, Affiliated Zhongda Hospital, Southeast University Medical School, 87 Ding Jia Qiao Road, Nanjing, 210089, Jiangsu, China
    2. Department of Surgery, Haian People’s Hospital, Nantong University Medical School, Nantong, 226600, Jiangsu, China
    3. Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, 210093, Jiangsu, China
  • 刊物类别:Medicine
  • 刊物主题:Medicine & Public Health
    Gastroenterology
    Hepatology
    Oncology
    Transplant Surgery
    Biochemistry
  • 出版者:Springer Netherlands
  • ISSN:1573-2568
文摘
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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