Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Clinical Medicine, The second School of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China.
Expert Opin Ther Targets. 2019 Dec;23(12):1015-1030. doi: 10.1080/14728222.2019.1696309. Epub 2019 Nov 28.
: Autoimmune diseases (ADs) are idiopathic and heterogeneous disorders with contentious pathophysiology. Great strides have been made in epigenetics and its involvement in ADs. Zeste homolog 2 (EZH2) has sparked extensive interest because of its pleiotropic roles in distinct pathologic contexts.: This review summarizes the epigenetic functions and the biological significance of EZH2 in the etiology of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), and systemic sclerosis (SSc). A brief recapitulation of the therapeutic potential of EZH2 targeting is provided.: There are questions marks and controversies surrounding the feasibility and safety of EZH2 targeting; it is recommended in RA and SLE, but queried in T1D, IBD, MS, and SSc. Future work should focus on contrast studies, systematic analyses and preclinical studies with optimizing methodologies. Selective research studies conducted in a stage-dependent manner are necessary because of the relapsing-remitting clinical paradigms.
自身免疫性疾病(AD)是特发性和异质性疾病,其发病机制存在争议。在表观遗传学及其在 AD 中的作用方面已经取得了重大进展。Zeste 同源物 2(EZH2)因其在不同病理环境中的多效性作用而引起了广泛的关注。
本综述总结了 EZH2 在类风湿关节炎(RA)、系统性红斑狼疮(SLE)、1 型糖尿病(T1D)、炎症性肠病(IBD)、多发性硬化症(MS)和系统性硬化症(SSc)发病机制中的表观遗传功能和生物学意义。简要回顾了 EZH2 靶向治疗的潜力。
EZH2 靶向治疗的可行性和安全性存在疑问和争议;在 RA 和 SLE 中推荐,但在 T1D、IBD、MS 和 SSc 中存在疑问。未来的工作应侧重于对比研究、系统分析和优化方法的临床前研究。由于存在复发缓解的临床模式,因此有必要进行分阶段进行的选择性研究。