Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University and Charlie Norwood VA Medical Center, Augusta, GA, USA.
Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, China.
Nat Rev Nephrol. 2019 Apr;15(4):220-239. doi: 10.1038/s41581-018-0103-6.
Acute kidney injury (AKI) is a major public health concern associated with high morbidity and mortality. Despite decades of research, the pathogenesis of AKI remains incompletely understood and effective therapies are lacking. An increasing body of evidence suggests a role for epigenetic regulation in the process of AKI and kidney repair, involving remarkable changes in histone modifications, DNA methylation and the expression of various non-coding RNAs. For instance, increases in levels of histone acetylation seem to protect kidneys from AKI and promote kidney repair. AKI is also associated with changes in genome-wide and gene-specific DNA methylation; however, the role and regulation of DNA methylation in kidney injury and repair remains largely elusive. MicroRNAs have been studied quite extensively in AKI, and a plethora of specific microRNAs have been implicated in the pathogenesis of AKI. Emerging research suggests potential for microRNAs as novel diagnostic biomarkers of AKI. Further investigation into these epigenetic mechanisms will not only generate novel insights into the mechanisms of AKI and kidney repair but also might lead to new strategies for the diagnosis and therapy of this disease.
急性肾损伤（AKI）是一个主要的公共卫生关注点，与高发病率和死亡率相关。尽管已经进行了数十年的研究，但 AKI 的发病机制仍不完全清楚，且缺乏有效的治疗方法。越来越多的证据表明，表观遗传调控在 AKI 和肾脏修复过程中起作用，涉及组蛋白修饰、DNA 甲基化和各种非编码 RNA 的表达的显著变化。例如，组蛋白乙酰化水平的增加似乎可以保护肾脏免受 AKI 的侵害并促进肾脏修复。AKI 还与全基因组和基因特异性 DNA 甲基化的变化相关；然而，DNA 甲基化在肾脏损伤和修复中的作用和调控仍在很大程度上难以捉摸。microRNAs 在 AKI 中已经得到了相当广泛的研究，并且大量特定的 microRNAs 被认为与 AKI 的发病机制有关。新兴的研究表明，microRNAs 可能成为 AKI 的新型诊断生物标志物。对这些表观遗传机制的进一步研究不仅将深入了解 AKI 和肾脏修复的机制，还可能为该疾病的诊断和治疗提供新策略。
