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急性肾损伤的表观遗传学靶向治疗

Epigenetic targeting for acute kidney injury.

作者信息

Zhuang Shougang

机构信息

Department of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, Rhode Island, USA.

Department of Nephrology, Shanghai East Hospital, Shanghai, China.

出版信息

Nephrology (Carlton). 2018 Oct;23 Suppl 4:21-25. doi: 10.1111/nep.13466.

Abstract

In recent years, epigenetics has emerged as important mechanisms for the regulation of pathogenesis in many diseases, including acute kidney injury (AKI). Numerous studies have demonstrated that AKI is associated with the changes in epigenetics, including histone modifications, DNA methylation and the expression of various non-coding RNAs. Through utilizing histone deacetylase (HDAC) inhibitors, studies have demonstrated that increase of histone acetylation either protects kidney from injury or potentiates this process, depending on which HDAC (s) isform is suppressed, whereas inhibition of histone methyltransferase, generally provides a protective effect in AKI. Although AKI is also associated with changes in DNA methylation, the role of DNA methylation in kidney injury remains unclear. In this article, we discuss the role and mechanism of histone acetylation and methylation in the pathogenesis of AKI.

摘要

近年来,表观遗传学已成为包括急性肾损伤(AKI)在内的许多疾病发病机制调控的重要机制。大量研究表明,AKI与表观遗传学变化有关,包括组蛋白修饰、DNA甲基化以及各种非编码RNA的表达。通过使用组蛋白去乙酰化酶(HDAC)抑制剂,研究表明组蛋白乙酰化的增加要么保护肾脏免受损伤,要么增强这一过程,这取决于抑制的是哪种HDAC亚型,而组蛋白甲基转移酶的抑制通常在AKI中具有保护作用。虽然AKI也与DNA甲基化的变化有关,但DNA甲基化在肾损伤中的作用仍不清楚。在本文中,我们讨论了组蛋白乙酰化和甲基化在AKI发病机制中的作用和机制。

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