组蛋白甲基转移酶EZH2：肾脏疾病的潜在治疗靶点。
Histone Methyltransferase EZH2: A Potential Therapeutic Target for Kidney Diseases.
作者信息
Li Tingting, Yu Chao, Zhuang Shougang
机构信息
Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Medicine, Alpert Medical School and Rhode Island Hospital, Brown University, Providence, RI, United States.
出版信息
Front Physiol. 2021 Feb 18;12:640700. doi: 10.3389/fphys.2021.640700. eCollection 2021.
Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme that catalyzes the addition of methyl groups to histone H3 at lysine 27, leading to gene silencing. Mutation or over-expression of EZH2 has been linked to many cancers including renal carcinoma. Recent studies have shown that EZH2 expression and activity are also increased in several animal models of kidney injury, such as acute kidney injury (AKI), renal fibrosis, diabetic nephropathy, lupus nephritis (LN), and renal transplantation rejection. The pharmacological and/or genetic inhibition of EZH2 can alleviate AKI, renal fibrosis, and LN, but potentiate podocyte injury in animal models, suggesting that the functional role of EZH2 varies with renal cell type and disease model. In this article, we summarize the role of EZH2 in the pathology of renal injury and relevant mechanisms and highlight EZH2 as a potential therapeutic target for kidney diseases.
zeste同源物2增强子（EZH2）是一种组蛋白赖氨酸N-甲基转移酶，可催化在组蛋白H3的赖氨酸27处添加甲基基团，导致基因沉默。EZH2的突变或过表达与包括肾癌在内的多种癌症有关。最近的研究表明，在几种肾损伤动物模型中，如急性肾损伤（AKI）、肾纤维化、糖尿病肾病、狼疮性肾炎（LN）和肾移植排斥反应，EZH2的表达和活性也会增加。EZH2的药理和/或基因抑制可减轻动物模型中的AKI、肾纤维化和LN，但会加重足细胞损伤，这表明EZH2的功能作用随肾细胞类型和疾病模型而变化。在本文中，我们总结了EZH2在肾损伤病理中的作用及相关机制，并强调EZH2作为肾脏疾病潜在治疗靶点的重要性。
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