Garud Mayuresh Sudamrao, Kulkarni Yogesh Anant
SPP School of Pharmacy & Technology Management, SVKM's NMIMS, Mumbai-56, India.
Curr Diabetes Rev. 2014 May;10(3):182-9. doi: 10.2174/1573399810666140606103645.
Nephropathy is one of the major complications of diabetes which further directs to end stage renal disease. Extensive work has been done to find out the mechanisms involved in pathogenesis of the DN. Now, many researchers have been convinced that almost all of the molecular mediators and intracellular signaling pathways involved in progression of diabetic nephropathy have involvement in transforming growth factor beta (TGF- β) at some stage. In DN, hyperglycemia causes increase in the expression of TGF- β genes, TGF- β proteins and their receptors. Increased glucose level mediates these effects through activation of polyol pathway, protein kinase C pathway, hexosamine pathway, increases advanced glycation end products (AGE) and increases oxidative stress. Hyperglycemia also activates the TGF- β via activation of glucose transporters (GLUT), angiotensine II and platelet derived growth factor (PDGF). Activated TGF-β further leads to glomerular basement membrane (GBM) thickening and glomerulosclerosis through activation of connective tissue growth factor (CDGF) and vascular endothelial growth factor (VEGF). We have discussed the progression of hyperglycemia to DN via TGF- β, whose schematic presentation may serve as an effective way to understand the mechanisms and to find out an effective way for the management of diabetic nephropathy.
肾病是糖尿病的主要并发症之一，可进一步发展为终末期肾病。人们已经开展了大量工作来探究糖尿病肾病发病机制中涉及的相关机制。如今，许多研究人员确信，几乎所有参与糖尿病肾病进展的分子介质和细胞内信号通路在某个阶段都与转化生长因子β（TGF-β）有关。在糖尿病肾病中，高血糖会导致TGF-β基因、TGF-β蛋白及其受体的表达增加。血糖水平升高通过激活多元醇途径、蛋白激酶C途径、己糖胺途径、增加晚期糖基化终产物（AGE）以及增加氧化应激来介导这些效应。高血糖还通过激活葡萄糖转运蛋白（GLUT）、血管紧张素II和血小板衍生生长因子（PDGF）来激活TGF-β。激活的TGF-β通过激活结缔组织生长因子（CDGF）和血管内皮生长因子（VEGF）进一步导致肾小球基底膜（GBM）增厚和肾小球硬化。我们已经讨论了高血糖通过TGF-β发展为糖尿病肾病的过程，其示意图展示可能是理解相关机制以及找到糖尿病肾病有效管理方法的有效途径。
