Department of Biochemistry, King George's Medical University, U.P., Lucknow, India.
Department of Medicine, King George's Medical University, U.P., Lucknow, India.
Diabetes Metab Res Rev. 2019 Jul;35(5):e3155. doi: 10.1002/dmrr.3155. Epub 2019 Apr 3.
Diabetic kidney disease is one of the most serious microvascular complications and among the leading causes of end stage renal disease. Persistently increasing albuminuria has been considered to be the central hallmark of nephropathy. However, albuminuria can indicate kidney damage for clinicians; it is not a specific biomarker for prediction of diabetic kidney disease prior to the onset of this devastating complication, and in fact all individuals with microalbuminuria do not progress to overt nephropathy. Controlled glycemia is unable to prevent nephropathy in all diabetic individuals indicating the role of other factors in progression of diabetic kidney disease. There are numerous cellular and molecular defects persisting prior to appearance of clinical symptoms. So, there is an urgent need to look for easy, novel, and accurate way to detect diabetic kidney disease prior to its beginning or at the infancy stage so that its progression can be slowed or arrested. It is now accepted that initiation and progression of diabetic kidney disease are a result of complex interactions between genetic and environmental factors. Environmental signals can alter the intracellular pathways by chromatin modifiers and regulate gene expression patterns leading to diabetes and its complications. In the present review, we have discussed a possible link between aberrant DNA methylation and altered gene expression in diabetic kidney disease. Drugs targeting to reverse epigenetic alteration can retard or stop the development of this devastating disease, just by breaking the chain of events occurring prior to the development of this microvascular complication in patients with diabetes.
糖尿病肾病是最严重的微血管并发症之一，也是终末期肾病的主要原因之一。持续增加的蛋白尿一直被认为是肾病的核心标志。然而，对于临床医生来说，蛋白尿只能表明肾脏受损；它并不是预测糖尿病肾病的特异性生物标志物，在这种破坏性并发症发生之前，事实上并非所有微量白蛋白尿患者都会进展为显性肾病。控制血糖并不能预防所有糖尿病患者的肾病，这表明其他因素在糖尿病肾病的进展中起作用。在出现临床症状之前，就存在许多持续存在的细胞和分子缺陷。因此，迫切需要寻找一种简单、新颖、准确的方法，在糖尿病肾病开始或处于早期阶段时进行检测，以便减缓或阻止其进展。现在人们已经认识到，糖尿病肾病的发生和进展是遗传和环境因素之间复杂相互作用的结果。环境信号可以通过染色质修饰物改变细胞内途径，并调节基因表达模式，导致糖尿病及其并发症的发生。在本综述中，我们讨论了糖尿病肾病中异常 DNA 甲基化与基因表达改变之间可能存在的联系。针对表观遗传改变的药物可以通过阻断糖尿病患者微血管并发症发生前的一系列事件，延缓或阻止这种破坏性疾病的发展。
