Lu Heng-Cheng, Dai Wen-Ni, He Li-Yu
Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, People's Republic of China.
Diabetes Metab Syndr Obes. 2021 Jan 22;14:329-344. doi: 10.2147/DMSO.S288500. eCollection 2021.
Diabetic kidney disease (DKD), as the main complication of diabetes mellitus, is the primary cause of the end-stage renal disease (ESRD) and the most common chronic kidney disease. Overall, 30-40% of patients with type 1 and type 2 diabetes eventually develop DKD. Although some diabetes patients have intensified glycemic control, they still develop diabetic kidney disease. Current treatment methods can alleviate but do not markedly halt disease development, resulting in renal failure and severe complications, even contributing to elevated morbidity and mortality rates. DKD is a disease with interactions of genes and the environment. Emerging evidence indicates that DKD-associated key genes are also regulated by the epigenetic mechanism. Recently, increasing researches involving cells and experimental animals demonstrated that histone post-translational modifications can mediate gene expression, which correlated with diabetic kidney disease. Novel therapeutic strategies for epigenetic events could be beneficial for the early detection and treatment of DKD to prevent it from developing into end-stage renal disease (ESRD). In this review, we discuss prior findings in the field of histone modifications in DKD, especially histone acetylation and histone methylation. We then focus on recent developments in histone acetylation and methylation involved in the pathogenesis of DKD.
糖尿病肾病(DKD)作为糖尿病的主要并发症,是终末期肾病(ESRD)的主要病因,也是最常见的慢性肾脏病。总体而言,1型和2型糖尿病患者中有30%-40%最终会发展为DKD。尽管一些糖尿病患者加强了血糖控制,但仍会患上糖尿病肾病。目前的治疗方法可以缓解病情,但不能显著阻止疾病发展,最终导致肾衰竭和严重并发症,甚至导致发病率和死亡率升高。DKD是一种基因与环境相互作用的疾病。新出现的证据表明,与DKD相关的关键基因也受表观遗传机制调控。最近,越来越多涉及细胞和实验动物的研究表明,组蛋白翻译后修饰可介导基因表达,这与糖尿病肾病相关。针对表观遗传事件的新型治疗策略可能有助于DKD的早期检测和治疗,以防止其发展为终末期肾病(ESRD)。在本综述中,我们讨论了DKD领域中组蛋白修饰的先前研究结果,尤其是组蛋白乙酰化和组蛋白甲基化。然后,我们重点关注参与DKD发病机制的组蛋白乙酰化和甲基化的最新进展。