title: Vitamin D prevents the intestinal fibrosis via induction of vitamin D receptor and inhibition of transforming growth factor-beta1/Smad3 pathway.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of General Surgery, Affiliated Zhongda Hospital, Southeast University Medical School, 87 Ding Jia Qiao Road, Nanjing, 210089, Jiangsu, China, taoqs_nju@hotmail.com.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tao
authors.forename: Baochai
authors.initials: B
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Pan
authors.forename: Jianan
authors.initials: J
authors.lastname: Ren
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011897:Random Allocation; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000150:complications / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D014807:Vitamin D