Epigenetic Alterations in Podocytes in Diabetic Nephropathy.
Epigenetic Alterations in Podocytes in Diabetic Nephropathy.
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DOI：
10.3389/fphar.2021.759299
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发表时间：
2021
影响因子：
5.6
通讯作者：
Itoh H
中科院分区：
文献类型：
--
作者：
Sugita E;Hayashi K;Hishikawa A;Itoh H
近年来，表观遗传改变已被证明参与糖尿病及其并发症的发病机制。肾足细胞是肾小球上皮细胞，是形成裂隙膜的重要细胞，裂隙膜是蛋白尿的屏障。足细胞是终末分化的细胞，没有细胞分裂或补充能力。因此，足细胞损伤是决定肾脏预后的关键因素之一。最近的研究，包括我们的研究，表明足细胞的表观遗传变化与慢性肾脏疾病，包括糖尿病肾病有关。此外，DNA损伤修复和糖尿病足细胞的表观遗传变化之间的关系已经得到证实。利用人体样本（如肾活检和尿源性细胞）检测足细胞DNA损伤和表观遗传变化，可能是估计糖尿病患者肾脏损伤和肾脏预后的一种有前途的策略。靶向表观遗传足细胞改变和相关DNA损伤可能成为预防终末期肾病（ESRD）进展的一种新的治疗策略，并可能为糖尿病肾病提供预后标志物。本文综述了糖尿病肾病足细胞表观遗传变化的最新进展，特别是DNA甲基化，并讨论了这些变化在人类样本中的检测。此外，我们关注DNA损伤，DNA损伤在高糖条件下增加，并与足细胞表观遗传变化的产生有关。此外，还讨论了糖尿病的表观遗传记忆。考虑到老龄化社会中糖尿病肾病患者人数的增加，了解足细胞表观遗传变化在糖尿病肾病中的作用可能是非常重要的。
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.
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