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糖尿病肾病足细胞损伤中的组蛋白修饰。

Histone modification in podocyte injury of diabetic nephropathy.

机构信息

Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, 250012, Shandong, China.

Department of Nephrology, Shandong Provincial Hospital, Shandong First Medical University, No. 324 Jingwu Street, Jinan, 250021, Shandong, China.

出版信息

J Mol Med (Berl). 2022 Oct;100(10):1373-1386. doi: 10.1007/s00109-022-02247-7. Epub 2022 Aug 30.

Abstract

Diabetic nephropathy (DN), an important complication of diabetic microvascular disease, is one of the leading causes of end-stage renal disease (ESRD), which brings heavy burdens to the whole society. Podocytes are terminally differentiated glomerular cells, which act as a pivotal component of glomerular filtration barrier. When podocytes are injured, glomerular filtration barrier is damaged, and proteinuria would occur. Dysfunction of podocytes contributes to DN. And degrees of podocyte injury influence prognosis of DN. Growing evidences have shown that epigenetics does a lot in the evolvement of podocyte injury. Epigenetics includes DNA methylation, histone modification, and non-coding RNA. Among them, histone modification plays an indelible role. Histone modification includes histone methylation, histone acetylation, and other modifications such as histone phosphorylation, histone ubiquitination, histone ADP-ribosylation, histone crotonylation, and histone β-hydroxybutyrylation. It can affect chromatin structure and regulate gene transcription to exert its function. This review is to summarize documents about pathogenesis of podocyte injury, most importantly, histone modification of podocyte injury in DN recently to provide new ideas for further molecular research, diagnosis, and treatment.

摘要

糖尿病肾病(DN)是糖尿病微血管病变的重要并发症之一,是终末期肾病(ESRD)的主要原因之一,给整个社会带来了沉重的负担。足细胞是终末分化的肾小球细胞,是肾小球滤过屏障的关键组成部分。当足细胞受损时,肾小球滤过屏障受损,就会出现蛋白尿。足细胞功能障碍导致 DN。足细胞损伤的程度影响 DN 的预后。越来越多的证据表明,表观遗传学在足细胞损伤的演变中起着重要作用。表观遗传学包括 DNA 甲基化、组蛋白修饰和非编码 RNA。其中,组蛋白修饰起着不可磨灭的作用。组蛋白修饰包括组蛋白甲基化、组蛋白乙酰化等修饰,以及组蛋白磷酸化、组蛋白泛素化、组蛋白 ADP-核糖基化、组蛋白巴豆酰化和组蛋白 β-羟丁酸酰化等。它可以影响染色质结构,调节基因转录,从而发挥作用。本综述旨在总结有关足细胞损伤发病机制的文献,尤其是最近关于 DN 中足细胞损伤的组蛋白修饰,为进一步的分子研究、诊断和治疗提供新的思路。

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