Monocyte chemoattractant protein-1: does it play a role in diabetic nephropathy?
Monocyte chemoattractant protein-1: does it play a role in diabetic nephropathy?
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DOI：
10.1093/ndt/18.3.457
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发表时间：
2003-03
期刊：
影响因子：
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通讯作者：
T. Wada;H. Yokoyama;K. Matsushima;Ken‐ichi Kobayashi
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文献类型：
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作者：
T. Wada;H. Yokoyama;K. Matsushima;Ken‐ichi Kobayashi
代谢和血液动力学途径均影响糖尿病肾病的进展[1，2]。慢性高血糖、晚期糖基化终末产物（AGE）、山梨醇升高、蛋白激酶C（PKC）活化、肾小球高血压和遗传易感性已被确定为糖尿病肾病进展的危险因素[2]。此外，炎症细胞如单核巨噬细胞（Mf）浸润患病肾脏是糖尿病肾病的标志[3，4]。浸润的Mf释放溶酶体酶、一氧化二氮（NO）、活性氧中间体（ROI）和转化生长因子（TGF）-B，它们在肾损伤中起重要作用[2，5]。单核细胞趋化蛋白（MCP）-1，又称单核细胞趋化和活化因子（MCAF）或CCL 2，是由单核细胞和各种非白细胞（包括肾驻留细胞）分泌的一种趋化因子。在实验性肾小球肾炎模型[6-8]和人肾炎[9-11]中，认为其通过Mf募集和活化在新月体形成和进行性肾小管间质病变的发病机制中起重要作用。除了这些炎症性肾脏疾病外，最近的研究表明MCP-1还参与糖尿病肾病。在这篇社论中，我们重点关注（i）MCP-1及其同源受体，CCR 2在人类糖尿病肾病中的作用，以及（ii）MCP-1uCCR 2在糖尿病肾病发病机制中的作用的体外和体内研究。研究结果表明，针对MCP-1uCCR 2系统的干预措施是治疗糖尿病肾病的潜在策略。MCP-1uCCR 2与糖尿病肾病
Both metabolic and haemodynamic pathways impact on the progressionof diabetic nephropathy [1,2]. Chronic hyperglycaemia, advanced glycation end (AGE) products, increase of sorbitol, activation of protein kinase C (PKC), glomerular hypertension and genetic susceptibility have been identified as risk factors in the progression of diabetic nephropathy [2]. Moreover, infiltration of the diseased kidneys by inflammatory cells such as monocytesumacrophages (Mf) is a hallmark of diabetic nephropathy [3,4]. Infiltrated Mf release lysosomal enzymes, nitrous oxide (NO), reactive oxygen intermediates (ROI) and transforming growth factor (TGF)-b, which play an essential role in renal damage [2,5]. A chemokine, monocyte chemoattractant protein (MCP)-1, also termed monocyte chemotactic and activating factor (MCAF) or CCL2, is secreted bymononuclear cells and various non-leukocytic cells including renal resident cells. In experimental glomerulonephritis models [6–8] and human nephritis [9–11] it is thought to play an important role in the pathogenesis of crescent formation and progressive tubulointerstitial lesions via Mf recruitment and activation. In addition to these inflammatory renal diseases, recent studies suggest that MCP-1 is also involved in diabetic nephropathy. In this editorial comment we focus on (i) MCP-1 and its cognate receptor, CCR2 in human diabetic nephropathy, and (ii) in vitro and in vivo studies of the role of MCP-1uCCR2 in the pathogenesis of diabetic nephropathy. The findings suggest interventions targeting the MCP-1uCCR2 systems as potential strategies to treat diabetic nephropathy. MCP-1uCCR2 in human diabetic nephropathy