The synonymous single nucleotide polymorphism (SNP) rs731236, located in the vitamin D receptor (VDR) gene (Taq I) has been associated with both decreased levels of the protein in peripheral blood mononuclear cells and a fibrosis-related complication in Crohn´s disease (CD). Interactions between VDR and a protein-disulfide isomerase-associated 3 (PDIA3) in the regulation of extracellular matrix have been reported and we aim to analyze the relevance of the VDR genotypes and the effects of Vitamin D (VD) in the expression of VDR, PDIA3 and proliferation of intestinal fibroblasts. Human intestinal fibroblasts were isolated from the non-affected surgical resections of colorectal patients and classified according to the VDR genotype. In some cases, cells were transfected with specific PDIA3 siRNA. Basal and VD-stimulated expression of VDR, PDIA3 and Collagen 1A1 (COL1A1) as well as fibroblast migration/proliferation were analyzed. Our data show that intestinal fibroblasts homozygous for the C allele in the VDR gene exhibited lower VDR protein levels and higher proliferation than cells homozygous for the T allele. VD increased VDR and attenuated the accelerated proliferation of CC fibroblasts. The diminished VDR level detected in CC cells was associated with increased levels of both PDIA3 and COL1A1 expression and the transient silencing of PDIA3 significantly reduced COL1A1 expression. We conclude that intestinal fibroblasts homozygous for the C allele in the VDR gene exhibited: reduced VDR protein levels, increased proliferation and increased PDIA3/COL1A1 expression. Treatment with VD increased VDR and attenuated proliferation of these cells.

位于维生素D受体（VDR）基因（Taq I）中的同义单核苷酸多态性（SNP）rs731236与外周血单核细胞中蛋白质水平的降低以及克罗恩病中与纤维化相关的并发症有关（光盘）。已经报道了VDR和蛋白质二硫键异构酶相关3（PDIA3）在细胞外基质调控中的相互作用，我们旨在分析VDR基因型的相关性以及维生素D（VD）在VDR表达中的作用， PDIA3与肠成纤维细胞的增殖。从未受影响的结直肠患者手术切除物中分离出人肠道成纤维细胞，并根据VDR基因型进行分类。在某些情况下，用特异性PDIA3 siRNA转染细胞。VDR的基础和VD刺激表达，分析了PDIA3和胶原1A1（COL1A1）以及成纤维细胞的迁移/增殖。我们的数据显示，与T等位基因纯合的细胞相比，VDR基因中C等位基因纯合的肠道成纤维细胞显示出更低的VDR蛋白水平和更高的增殖。VD增加VDR并减弱CC成纤维细胞的加速增殖。CC细胞中检测到的VDR水平降低与PDIA3和COL1A1表达水平升高相关，而PDIA3的瞬时沉默则显着降低了COL1A1表达水平。我们得出结论，在VDR基因中C等位基因纯合的肠成纤维细胞表现出：VDR蛋白水平降低，增殖增加和PDIA3 / COL1A1表达增加。VD处理可增加VDR并减弱这些细胞的增殖。