Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, 3004, Australia.
Curr Diab Rep. 2013 Aug;13(4):574-81. doi: 10.1007/s11892-013-0383-y.
A strong case for the deregulation of epigenetic chromatin modifications in the development and progression of various chronic complications of diabetes has emerged from recent experimental observations. Clinical trials of type 1 and type 2 diabetes patients highlight the importance of early and intensive treatment and the prolonged damage of hyperglycemia on organs such as the kidney. The functional relationship between the regulation of chromatin architecture and persistent gene expression changes conferred by prior hyperglycemia represents an important avenue of investigation for explaining diabetic nephropathy. While several studies implicate epigenetic changes at the chromatin template in the deregulated gene expression associated with diabetic nephropathy, the molecular determinants of metabolic memory in renal cells remain poorly understood. There is now strong evidence from experimental animals and cell culture of persistent glucose-driven changes in vascular endothelial gene expression that may also have relevance for the microvasculature of the kidney. Exploration of epigenetic mechanisms underlying the hyperglycemic cue mediating persistent transcriptional changes in renal cells holds novel therapeutic potential for diabetic nephropathy.
近年来的实验观察结果表明，表观遗传染色质修饰在各种糖尿病慢性并发症的发生和发展中存在去调控的强有力证据。1 型和 2 型糖尿病患者的临床试验强调了早期和强化治疗以及高血糖对肾脏等器官的长期损害的重要性。染色质结构调节与先前高血糖引起的持续基因表达变化之间的功能关系，代表了一种重要的研究途径，可以解释糖尿病肾病。虽然有几项研究表明，在与糖尿病肾病相关的基因表达失调中，染色质模板上的表观遗传变化，但在肾细胞中，代谢记忆的分子决定因素仍知之甚少。目前，来自实验动物和细胞培养的强有力证据表明，血管内皮基因表达存在持续的葡萄糖驱动变化，这也可能与肾脏的微血管有关。探索高血糖信号介导肾细胞持续转录变化的表观遗传机制，为糖尿病肾病提供了新的治疗潜力。
