Majumder Syamantak, Advani Andrew
Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
J Diabetes Complications. 2015 Nov-Dec;29(8):1337-44. doi: 10.1016/j.jdiacomp.2015.07.015. Epub 2015 Jul 17.
Chronic hyperglycemia early in the course of diabetes confers a sustained increase in the risk of complications development. In recent years, efforts to understand the molecular basis for this "metabolic memory" have focused on epigenetic mechanisms as a means by which transient high glucose can cause persistent and propagated changes in cell function. For instance, in vascular endothelial cells, smooth muscle cells and peripheral blood cells, temporary exposure to high glucose causes changes in epigenetic marks that promote a shift towards a pro-inflammatory phenotype. However, the influence of epigenetic processes in complications development extends beyond their contribution to metabolic memory. Podocytes, for example, are terminally differentiated cells of the renal glomerulus whose injury is a major contributor to the pathogenesis of nephropathy. Over recent months, several reports have emerged describing the essential actions of histone-modifying enzymes and DNA methylation patterns (the two principal epigenetic mechanisms) in maintaining podocyte integrity, especially under diabetic conditions. Here, we review the known and potential role of epigenetic processes within podocytes, focusing on the evidence linking these processes to oxidative stress, crosstalk with tubule cells, autophagy and slit-pore protein expression. Whether podocytes themselves exhibit a metabolic memory awaits to be seen.
糖尿病病程早期的慢性高血糖会使并发症发生风险持续增加。近年来，为了解这种“代谢记忆”的分子基础所做的努力聚焦于表观遗传机制，认为这是短暂高血糖导致细胞功能发生持续且广泛变化的一种方式。例如，在血管内皮细胞、平滑肌细胞和外周血细胞中，短暂暴露于高血糖会导致表观遗传标记发生变化，促使细胞向促炎表型转变。然而，表观遗传过程对并发症发生的影响不仅限于其对代谢记忆的作用。例如，足细胞是肾小球的终末分化细胞，其损伤是肾病发病机制的主要因素。近几个月来，有几份报告描述了组蛋白修饰酶和DNA甲基化模式（两种主要的表观遗传机制）在维持足细胞完整性方面的重要作用，尤其是在糖尿病条件下。在此，我们综述足细胞内表观遗传过程已知的和潜在的作用，重点关注将这些过程与氧化应激、与肾小管细胞的相互作用、自噬以及裂孔蛋白表达联系起来的证据。足细胞本身是否表现出代谢记忆还有待观察。
