Monocyte chemoattractant protein-1: does it play a role in diabetic nephropathy?

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