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创伤愈合和纤维化的表观遗传调控。

Epigenetic regulation of wound healing and fibrosis.

机构信息

Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

出版信息

Curr Opin Rheumatol. 2013 Jan;25(1):101-7. doi: 10.1097/BOR.0b013e32835b13e1.

Abstract

PURPOSE OF REVIEW

Wound healing is a normal physiological response to tissue injury which can occur in any organ. Mechanisms that orchestrate wound healing in different organs are surprisingly generic, involving generation of fibroblasts and myofibroblasts by differentiation processes that require extensive alterations in gene expression. This process and indeed phenotype of cells are orchestrated by the combined influences of molecular components of epigenome including DNA methylation, vast array of posttranslational modifications of the histone protein constituents of chromatin and regulatory noncoding RNAs of which microRNAs (miRs) are the most extensively studied.

RECENT FINDINGS

Numerous studies from the last 12 months show all the three epigenetic mechanisms to be regulating generation and apoptosis of myofibroblasts in organs affected by perturbed wound healing. Furthermore, these mechanisms are involved in fibrotic disease itself, with some miRs and epigenetic drugs being tested for their therapeutic potential.

SUMMARY

Fields of wound healing and fibrosis will be enriched over the next decade by plethora of new information regarding epigenetic control mechanisms which will hopefully provide new advances in diagnostics and prognostics. With the design of ever more specific epigenetic drugs, we may improve our ability to therapeutically optimize wound healing and prevent fibrosis in chronic disease and ageing.

摘要

目的综述

伤口愈合是一种组织损伤的正常生理反应,可发生在任何器官。协调不同器官伤口愈合的机制非常相似,涉及通过需要广泛改变基因表达的分化过程产生成纤维细胞和成肌纤维细胞。这一过程,甚至细胞的表型,都受到包括 DNA 甲基化在内的表观基因组分子成分的综合影响,大量组蛋白蛋白组成染色质的翻译后修饰和调控非编码 RNA,其中 microRNAs(miRs)是研究最广泛的。

最新发现

过去 12 个月的大量研究表明,所有三种表观遗传机制都在调节受干扰伤口愈合影响的器官中成肌纤维细胞的生成和凋亡。此外,这些机制本身也与纤维化疾病有关,一些 microRNAs 和表观遗传药物正在测试其治疗潜力。

总结

在未来十年中,有关表观遗传调控机制的大量新信息将丰富伤口愈合和纤维化领域,有望为诊断和预后提供新的进展。随着越来越多的特异性表观遗传药物的设计,我们可能会提高我们治疗性优化伤口愈合和预防慢性疾病和衰老中纤维化的能力。

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