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DNA methylation in fibrosis

机译:DNA甲基化在纤维化中

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摘要

Fibrosis is characterised by an exuberant wound healing response and the major cell type responsible is the myofibroblast. The myofibroblast is typified by excessive ECM production and contractile activity and is demarcated by alpha-smooth muscle actin expression. What has recently come to light is that the activation of the fibroblast to myofibroblast may be under epigenetic control, specifically methylation. Methylation of DNA is a conserved mechanism to precisely regulate gene expression in a specific context. Hypermethylation leads to gene repression and hypomethylation results in gene induction. Methylation abnormalities have recently been uncovered in fibrosis, both organ specific and widespread fibrosis. The fact that these methylation changes are rapid and reversible lends themselves amenable to therapeutic intervention. This review considers the role of methylation in fibrosis and the activation of the myofibroblasts and how this could be targeted for fibrosis. Fibrosis is of course currently intractable to therapeutics and is a leading cause of morbidity and mortality and is an urgent unmet clinical need. (C) 2016 Elsevier GmbH. All rights reserved.
机译:纤维化的特征是旺盛的伤口愈合反应,而负责的主要细胞类型是成肌纤维细胞。肌成纤维细胞的典型特征是过量的ECM产生和收缩活动,并以α平滑肌肌动蛋白表达为界。最近发现的是,成纤维细胞向成肌纤维细胞的活化可能处于表观遗传控制之下,特别是甲基化。 DNA的甲基化是一种在特定情况下精确调节基因表达的保守机制。甲基化过高导致基因抑制,而甲基化过低导致基因诱导。最近在器官特异性和广泛性纤维化的纤维化中发现了甲基化异常。这些甲基化变化迅速且可逆的事实使其自身易于进行治疗干预。这篇综述考虑了甲基化在纤维化和肌成纤维细胞活化中的作用,以及如何将其定位为纤维化。当然,纤维化目前对于治疗而言是难于治疗的,并且是发病率和死亡率的主要原因,并且是迫切未满足的临床需求。 (C)2016 Elsevier GmbH。版权所有。

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