Targeting the MCP-1/CCR2 System in Diabetic Kidney Disease
Targeting the MCP-1/CCR2 System in Diabetic Kidney Disease
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DOI：
10.2174/157016110793563816
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发表时间：
2010-11-01
影响因子：
4.5
通讯作者：
Gruden, Gabriella
中科院分区：
文献类型：
--
作者：
Giunti, Sara;Barutta, Federica;Gruden, Gabriella
糖尿病肾病是西方世界终末期肾衰竭的主要原因，并导致糖尿病患者的显著发病率和死亡率。虽然高血脂症和高血压是并发症发生的关键决定因素，但最近的研究表明，低度炎症反应也可能起作用。单核细胞趋化蛋白1（MCP-1），一种由肾细胞产生的强效趋化因子，已成为这一过程中非常重要的参与者。具体地，已经显示MCP-1在糖尿病动物的肾脏中过表达。此外，在伴随糖尿病的情况下，MCP-1敲除小鼠的功能和结构异常均得到改善。近年来，将MCP-1与肾损伤联系起来的细胞机制已被越来越多地描述，并且特别地，已变得明显的是，MCP-1不仅通过诱导单核细胞募集，而且通过直接激活驻留的肾细胞来促成肾损伤。本文综述了MCP-1在糖尿病肾病中作用的最重要进展以及未来潜在的治疗意义。
Diabetic nephropathy is the leading cause of end-stage renal failure in the Western World and accounts for significant morbidity and mortality in patients with diabetes. Although hyperglycaemia and hypertension are established key determinants in the development of the complication, recent studies suggest that a low-grade inflammatory response may also play a role. Monocyte Chemoattractant Protein 1 (MCP-1), a potent chemokine produced by renal cells, has emerged as a very important player in this process. Specifically, it has been shown that MCP-1 is overexpressed in the kidneys from diabetic animals. Furthermore, there is amelioration of both functional and structural abnormalities in MCP-1-knockout mice in the setting of concomitant diabetes. Over recent years the cellular mechanisms linking MCP-1 to kidney injury have been increasingly delineated and, in particular, it has become evident that MCP-1 contributes to the kidney damage not only by inducing mononuclear cell recruitment, but also by direct activation of resident renal cells. The present review focuses on the most significant advances in understanding the role of MCP-1 in diabetic kidney disease and future potential therapeutic implications.