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(4): 868-75, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25326845
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-ß1/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-ß1 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-ß1, Smad-3, p-Smad3 and Collagen I in SEMF. 1,25(OH)2D3-induced VDR expression and decreased TGF-ß1-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-ß1/Smad3 pathway in the SEMF via VDR induction.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina D
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Doenças Inflamatórias Intestinais
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Receptores de Calcitriol
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Proteína Smad3
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Fator de Crescimento Transformador beta1
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article