Ramahi Ahmad, Altorok Nezam, Kahaleh Bashar
Division of Rheumatology and Immunology, Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA.
Eur J Rheumatol. 2020 Oct;7(Suppl 3):S147-S156. doi: 10.5152/eurjrheum.2020.19112. Epub 2020 Jul 20.
There is growing evidence that implicates epigenetic modification in the pathogenesis of systemic sclerosis (SSc). The complexity of epigenetic regulation and its dynamic nature complicate the investigation of its role in the disease. We will review the current literature for factors that link epigenetics to SSc by discussing DNA methylation, histone acetylation and methylation, and non-coding RNAs (ncRNAs), particularly microRNA changes in endothelial cells, fibroblasts (FBs), and lymphocytes. These three cell types are significantly involved in the early stages and throughout the course of the disease and are particularly vulnerable to epigenetic regulation. The pathogenesis of SSc is likely related to modifications of the epigenome by environmental signals in individuals with a specific genetic makeup. The epigenome is an attractive therapeutic target; however, successful epigenetics-based treatments require a better understanding of the molecular mechanisms controlling the epigenome and its alteration in the disease.
越来越多的证据表明表观遗传修饰与系统性硬化症（SSc）的发病机制有关。表观遗传调控的复杂性及其动态性质使得研究其在该疾病中的作用变得复杂。我们将通过讨论DNA甲基化、组蛋白乙酰化和甲基化以及非编码RNA（ncRNA），特别是内皮细胞、成纤维细胞（FBs）和淋巴细胞中的微小RNA变化，来回顾当前将表观遗传学与SSc联系起来的因素的文献。这三种细胞类型在疾病的早期阶段和整个病程中都有显著参与，并且特别容易受到表观遗传调控的影响。SSc的发病机制可能与具有特定基因组成的个体中环境信号对表观基因组的修饰有关。表观基因组是一个有吸引力的治疗靶点；然而，基于表观遗传学的成功治疗需要更好地理解控制表观基因组的分子机制及其在疾病中的改变。
