Epigenetic modifications in the pathogenesis of diabetic nephropathy.
Epigenetic modifications in the pathogenesis of diabetic nephropathy.
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DOI：
10.1016/j.semnephrol.2013.05.006
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发表时间：
2013-07
影响因子：
3.3
通讯作者：
Natarajan, Rama
中科院分区：
文献类型：
--
作者：
Reddy, Marpadga A.;Park, Jung Tak;Natarajan, Rama
糖尿病肾病（DN）是终末期肾脏疾病的主要原因。糖尿病血管并发症如DN可在随后的血糖控制下继续发展，提示先前暴露于高血糖的代谢记忆。糖尿病通过激活多种信号通路和关键转录因子，导致病理基因的异常表达，从而深刻影响靶细胞的转录程序。新出现的证据表明，这些与糖尿病并发症和代谢记忆的病理生理相关的因素也可能受到染色质中DNA甲基化、组蛋白赖氨酸乙酰化和甲基化等表观遗传机制的影响。关键组蛋白修饰和相关组蛋白甲基转移酶和乙酰转移酶参与糖尿病肾病和血管细胞中炎症和促纤维化基因的调节。表观基因组谱分析方法的进展为糖尿病影响靶细胞的染色质状态和功能结局提供了新的见解。由于表观遗传变化可能是可逆的，它们可以为未来开发急需的DN新疗法提供机会。在这篇综述中，我们讨论了表观遗传学领域的最新进展及其与糖尿病血管并发症和DN发病机制的相关性。
Diabetic nephropathy (DN) is a leading cause of end stage renal disease. Diabetic vascular complications like DN can progress despite subsequent glycemic control, suggesting a metabolic memory of previous exposure to hyperglycemia. Diabetes profoundly impacts transcription programs in target cells through activation of multiple signaling pathways and key transcription factors leading to aberrant expression of pathological genes. Emerging evidence suggests that these factors associated with the pathophysiology of diabetic complications and metabolic memory might also be influenced by epigenetic mechanisms in chromatin such as DNA methylation, histone lysine acetylation and methylation. Key histone modifications and the related histone methyltransferases and acetyltransferases have been implicated in the regulation of inflammatory and pro-fibrotic genes in renal and vascular cells under diabetic conditions Advances in epigenome profiling approaches have provided novel insights into the chromatin states and functional outcomes in target cells affected by diabetes. Because epigenetic changes are potentially reversible, they can provide a window of opportunity for the development of much needed new therapies for DN in the future. In this review we discuss recent developments in the field of epigenetics and their relevance to diabetic vascular complications and DN pathogenesis.
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