Altorok Nezam, Almeshal Nawaf, Wang Yongqing, Kahaleh Bashar
Division of Rheumatology and Immunology and Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA.
Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA.
Rheumatology (Oxford). 2015 Oct;54(10):1759-70. doi: 10.1093/rheumatology/keu155. Epub 2014 Apr 16.
The objective of this review is to present evidence that supports the central role of epigenetic regulation in the pathogenesis of SSc. SSc is a complex autoimmune disease characterized by immune activation, fibrosis of the skin and internal organs and obliterative vasculopathy affecting predominantly the microvessels. Remarkable progress has been made in the past few years emphasizing the importance of epigenetic modifications in the pathogenesis of many disorders, including SSc. Current evidence demonstrates alterations in DNA methylation, histone code modifications and changes in microRNA (miRNA) expression levels in SSc cells. Recent reports have described the differential expression of numerous regulatory miRNAs in SSc, mainly in SSc fibroblasts, a number of which are important in TGF-β pathways and downstream signalling cascades. While studies to date have revealed the significant role of epigenetic modifications in the pathogenesis of SSc, the causal nature of epigenetic alterations in SSc pathogenesis remains elusive. Additional longitudinal and comprehensive epigenetic studies designed to evaluate the effect of environmental epigenetic factors on disease pathogenesis are needed.
本综述的目的是提供证据，支持表观遗传调控在系统性硬化症发病机制中的核心作用。系统性硬化症是一种复杂的自身免疫性疾病，其特征为免疫激活、皮肤和内脏器官纤维化以及主要影响微血管的闭塞性血管病变。在过去几年中取得了显著进展，强调了表观遗传修饰在包括系统性硬化症在内的许多疾病发病机制中的重要性。目前的证据表明，系统性硬化症细胞中存在DNA甲基化改变、组蛋白编码修饰以及微小RNA（miRNA）表达水平变化。最近的报告描述了系统性硬化症中许多调节性miRNA的差异表达，主要存在于系统性硬化症成纤维细胞中，其中一些在转化生长因子-β（TGF-β）途径和下游信号级联反应中起重要作用。虽然迄今为止的研究揭示了表观遗传修饰在系统性硬化症发病机制中的重要作用，但表观遗传改变在系统性硬化症发病机制中的因果性质仍不清楚。需要进行更多纵向和全面的表观遗传学研究，以评估环境表观遗传因素对疾病发病机制的影响。
