Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently
Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently
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DOI：
10.1136/gutjnl-2014-307024
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发表时间：
2015-05-01
期刊：
影响因子：
24.5
通讯作者：
Canbay, Ali
中科院分区：
文献类型：
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作者：
Beilfuss, Anja;Sowa, Jan-Peter;Canbay, Ali
目的非酒精性脂肪性肝病（NAFLD）与肥胖密切相关，是代谢综合征的一部分，与血清维生素D （VD）水平低有关。由于已知VD与转化生长因子(TGF)- β信号之间存在串扰，VD被认为是一种抗纤维化治疗方法。我们评估了VD、维生素D受体（VDR）与原发性人肝星状细胞（phHSC）肝纤维化和106例病态肥胖NAFLD患者之间的关系。结果VD治疗phHSC可通过vdr依赖性和vdr非依赖性机制改善tgf - β诱导的纤维化。在VDR基因内A1012G单核苷酸多态性的GG纯合细胞中，纤维化反应的减少被消除。与健康肝脏相比，NAFLD肝脏表达更高水平的VDR mRNA和VDR片段。在A1012G纯合GG的患者中，VDR mRNA较低，而携带G等位基因的患者中，促纤维化基因的表达较高。结论：VD可能是特定基因型VDR纤维化发病早期的抗纤维化治疗选择。已知的VDR多态性可能影响对VD治疗的反应。
Objective Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity and constitutes part of the metabolic syndrome, which have been associated with low serum vitamin D (VD). Due to known crosstalk between VD and transforming growth factor (TGF)-beta signalling, VD has been proposed as an antifibrotic treatment.Design We evaluated the association between VD, the vitamin D receptor (VDR) and liver fibrosis in primary human hepatic stellate cells (phHSC) and 106 morbidly obese patients with NAFLD.Results Treating phHSC with VD ameliorated TGF-beta-induced fibrogenesis via both VDR-dependent and VDR-independent mechanisms. Reduction of fibrogenic response was abolished in cells homozygous for GG at the A1012G single nucleotide polymorphisms within the VDR gene. Compared with healthy livers, NAFLD livers expressed higher levels of VDR mRNA and VDR fragments. VDR mRNA was lower in patients homozygous for GG at A1012G and expression of profibrogenic genes was higher in patients carrying the G allele.Conclusions VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment.