Sugita Erina, Hayashi Kaori, Hishikawa Akihito, Itoh Hiroshi
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Front Pharmacol. 2021 Sep 24;12:759299. doi: 10.3389/fphar.2021.759299. eCollection 2021.
Recently, epigenetic alterations have been shown to be involved in the pathogenesis of diabetes and its complications. Kidney podocytes, which are glomerular epithelial cells, are important cells that form a slit membrane-a barrier for proteinuria. Podocytes are terminally differentiated cells without cell division or replenishment abilities. Therefore, podocyte damage is suggested to be one of the key factors determining renal prognosis. Recent studies, including ours, suggest that epigenetic changes in podocytes are associated with chronic kidney disease, including diabetic nephropathy. Furthermore, the association between DNA damage repair and epigenetic changes in diabetic podocytes has been demonstrated. Detection of podocyte DNA damage and epigenetic changes using human samples, such as kidney biopsy and urine-derived cells, may be a promising strategy for estimating kidney damage and renal prognoses in patients with diabetes. Targeting epigenetic podocyte changes and associated DNA damage may become a novel therapeutic strategy for preventing progression to end-stage renal disease (ESRD) and provide a possible prognostic marker in diabetic nephropathy. This review summarizes recent advances regarding epigenetic changes, especially DNA methylation, in podocytes in diabetic nephropathy and addresses detection of these alterations in human samples. Additionally, we focused on DNA damage, which is increased under high-glucose conditions and associated with the generation of epigenetic changes in podocytes. Furthermore, epigenetic memory in diabetes is discussed. Understanding the role of epigenetic changes in podocytes in diabetic nephropathy may be of great importance considering the increasing diabetic nephropathy patient population in an aging society.
最近，表观遗传改变已被证明与糖尿病及其并发症的发病机制有关。肾足细胞是肾小球上皮细胞，是形成裂孔膜（蛋白尿屏障）的重要细胞。足细胞是终末分化细胞，没有细胞分裂或补充能力。因此，足细胞损伤被认为是决定肾脏预后的关键因素之一。包括我们的研究在内的最近研究表明，足细胞中的表观遗传变化与包括糖尿病肾病在内的慢性肾脏病有关。此外，糖尿病足细胞中DNA损伤修复与表观遗传变化之间的关联也已得到证实。使用人体样本（如肾活检和尿液来源细胞）检测足细胞DNA损伤和表观遗传变化，可能是评估糖尿病患者肾脏损伤和肾脏预后的一种有前景的策略。针对足细胞表观遗传变化及相关DNA损伤可能成为预防进展至终末期肾病（ESRD）的一种新型治疗策略，并为糖尿病肾病提供一种可能的预后标志物。本综述总结了糖尿病肾病中足细胞表观遗传变化（尤其是DNA甲基化）的最新进展，并探讨了在人体样本中检测这些改变的方法。此外，我们关注了在高糖条件下增加且与足细胞表观遗传变化产生相关的DNA损伤。此外，还讨论了糖尿病中的表观遗传记忆。考虑到老龄化社会中糖尿病肾病患者数量的增加，了解足细胞表观遗传变化在糖尿病肾病中的作用可能非常重要。
