1,25-dihydroxyvitamin D3 and its nuclear receptor repress human α1 (I) collagen expression and type I collagen formation.
1,25-dihydroxyvitamin D3 and its nuclear receptor repress human α1 (I) collagen expression and type I collagen formation.
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DOI：
10.1111/liv.12122
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Mezey E
中科院分区：
文献类型：
--
作者：
Potter JJ;Liu X;Koteish A;Mezey E
维生素D缺乏症在慢性肝病中很常见，特别是在严重肝纤维化的患者中。目的：研究1，25-二羟维生素D3（1，25-（OH）2D 3）对人α1（I）胶原启动子和人星形LX-2细胞胶原形成的影响，并探讨维生素D受体（VDR）对启动子作用的机制。通过测量胶原mRNA和胶原蛋白以及通过转染实验来评估I型胶原。通过EMSA和ChIP试验测定VDR与α1（I）胶原启动子的结合。1，25-（OH）2D 3可减少人α1（I）胶原mRNA和蛋白以及星状细胞在接触TGFβ1后分泌I型胶原。此外，1，25-（OH）2D 3抑制TGFβ1诱导的转染LX-2细胞中α1（I）胶原启动子的激活。1，25-（OH）2D 3的作用是由VDR介导的，其在近端Sp1位点结合，也在胶原启动子上新鉴定的远端位点结合。VDR表达载体降低了转染LX-2细胞中胶原启动子的活性。1，25-（OH）2D 3抑制人星状细胞中I型胶原的形成。1，25-（OH）2D 3的作用由其受体介导，该受体结合在近端Sp1.1位点和胶原启动子上新鉴定的远端位点。纠正慢性肝病患者的维生素D缺乏是抑制纤维化进展的潜在疗法。
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)2D3) on the human α1(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. Type I collagen was assessed by measurements of collagen mRNA and collagen protein and by transfection experiments. Binding of VDR to the α1(I) collagen promoter was determined by EMSA and ChIP assays. 1,25-(OH)2D3 decreased human α1(I) collagen mRNA and protein and the secretion of type I collagen by stellate cells after exposure to TGFβ1. Furthermore, 1,25-(OH)2D3 inhibited TGFβ1–induced activation of the α1(I) collagen promoter in transfected LX-2 cells. The effect of 1, 25-(OH)2D3 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. 1,25-(OH)2D3 inhibits type I collagen formation in human stellate cells. The effect of 1,25-(OH)2D3 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.
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发表时间：
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影响因子：
4.5
作者：
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发表时间：
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期刊：
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作者：
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通讯作者：
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作者：
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