Nemtsova Marina V, Zaletaev Dmitry V, Bure Irina V, Mikhaylenko Dmitry S, Kuznetsova Ekaterina B, Alekseeva Ekaterina A, Beloukhova Marina I, Deviatkin Andrei A, Lukashev Alexander N, Zamyatnin Andrey A
Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Laboratory of Epigenetics, Research Centre for Medical Genetics, Moscow, Russia.
Front Genet. 2019 Jun 14;10:570. doi: 10.3389/fgene.2019.00570. eCollection 2019.
Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects about 1% of the world's population. The etiology of RA remains unknown. It is considered to occur in the presence of genetic and environmental factors. An increasing body of evidence pinpoints that epigenetic modifications play an important role in the regulation of RA pathogenesis. Epigenetics causes heritable phenotype changes that are not determined by changes in the DNA sequence. The major epigenetic mechanisms include DNA methylation, histone proteins modifications and changes in gene expression caused by microRNAs and other non-coding RNAs. These modifications are reversible and could be modulated by diet, drugs, and other environmental factors. Specific changes in DNA methylation, histone modifications and abnormal expression of non-coding RNAs associated with RA have already been identified. This review focuses on the role of these multiple epigenetic factors in the pathogenesis and progression of the disease, not only in synovial fibroblasts, immune cells, but also in the peripheral blood of patients with RA, which clearly shows their high diagnostic potential and promising targets for therapy in the future.
类风湿性关节炎(RA)是一种全身性自身免疫性疾病,影响着全球约1%的人口。RA的病因尚不清楚。人们认为它是在遗传和环境因素存在的情况下发生的。越来越多的证据表明,表观遗传修饰在RA发病机制的调节中起着重要作用。表观遗传学导致可遗传的表型变化,这些变化不是由DNA序列的变化决定的。主要的表观遗传机制包括DNA甲基化、组蛋白修饰以及由微小RNA和其他非编码RNA引起的基因表达变化。这些修饰是可逆的,可以通过饮食、药物和其他环境因素进行调节。与RA相关的DNA甲基化、组蛋白修饰和非编码RNA的异常表达的具体变化已经被确定。本综述重点关注这些多种表观遗传因素在疾病发病机制和进展中的作用,不仅在滑膜成纤维细胞、免疫细胞中,而且在RA患者的外周血中,这清楚地显示了它们在未来具有很高的诊断潜力和有前景的治疗靶点。