BACKGROUND: Vitamin D deficiency is common in chronic liver disease particularly in those with severe liver fibrosis. AIMS: To determine the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ) on the human α(1) (I) collagen promoter and collagen formation by human stellate LX-2 cells and the mechanism of the effect of the vitamin D receptor (VDR) on the promoter. METHODS: Type I collagen was assessed by measurements of collagen mRNA and collagen protein and by transfection experiments. Binding of VDR to the α(1) (I) collagen promoter was determined by EMSA and ChIP assays. RESULTS: 1,25-(OH)2 D3 decreased human α(1) (I) collagen mRNA and protein and the secretion of type I collagen by stellate cells after exposure to TGFβ1. Furthermore, 1,25-(OH)2 D3 inhibited TGFβ1-induced activation of the α(1) (I) collagen promoter in transfected LX-2 cells. The effect of 1,25-(OH)2 D3 is mediated by the VDR, which binds at a proximal Sp1 site and also at a newly identified distal site on the collagen promoter. A VDR expression vector reduced the activities of the collagen promoter in transfected LX-2 cells. CONCLUSIONS: 1,25-(OH)2 D3 inhibits type I collagen formation in human stellate cells. The effect of 1,25-(OH)2 D3 is mediated by its receptor which binds at a proximal Sp1.1 site and at a newly identified distal site on the collagen promoter. Correction of vitamin D deficiency in patients with chronic liver disease is a potential therapy to inhibit progression of fibrosis.
BACKGROUND:Vitamin Ddeficiency is common in chronic liver disease particularly in those with severe liver fibrosis. AIMS: To determine the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ) on the human α(1) (I) collagen promoter and collagen formation by human stellate LX-2 cells and the mechanism of the effect of the vitamin D receptor (VDR) on the promoter. METHODS: Type I collagen was assessed by measurements of collagen mRNA and collagen protein and by transfection experiments. Binding of VDR to the α(1) (I) collagen promoter was determined by EMSA and ChIP assays. RESULTS: 1,25-(OH)2 D3 decreased human α(1) (I) collagen mRNA and protein and the secretion of type I collagen by stellate cells after exposure to TGFβ1. Furthermore, 1,25-(OH)2 D3 inhibited TGFβ1-induced activation of the α(1) (I) collagen promoter in transfected LX-2 cells. The effect of 1,25-(OH)2 D3 is mediated by the VDR, which binds at a proximal Sp1 site and also at a newly identified distal site on the collagen promoter. A VDRexpression vector reduced the activities of the collagen promoter in transfected LX-2 cells. CONCLUSIONS: 1,25-(OH)2 D3 inhibits type I collagen formation in human stellate cells. The effect of 1,25-(OH)2 D3 is mediated by its receptor which binds at a proximal Sp1.1 site and at a newly identified distal site on the collagen promoter. Correction of vitamin Ddeficiency in patients with chronic liver disease is a potential therapy to inhibit progression of fibrosis.
Authors: J P Iredale; R C Benyon; J Pickering; M McCullen; M Northrop; S Pawley; C Hovell; M J Arthur Journal: J Clin Invest Date: 1998-08-01 Impact factor: 14.808
Authors: Samar R El Khoudary; Saad Samargandy; Irfan Zeb; Temitope Foster; Ian H de Boer; Dong Li; Matthew J Budoff Journal: Nutr Metab Cardiovasc Dis Date: 2019-09-10 Impact factor: 4.222