Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy

Background. Monocyte chemoattractant protein-1 (MCP-1) is a specific chemok ine to recruit and activate monocytes from the circulation to inflammatory site. In diabetic nephropathy, similar to other glomerulonephropathies. inf iltration and activation of monocytes/macrophages in glomerulus have been i mplicated in the development of glomerular injury. The aim of the present s tudy was to examine a possible relationship of MCP-1 with diabetic nephropa thy and to investigate the role of glycated albumin (Gly-Alb) as well as hi gh concentration of glucose (HG) on MCP-1 production by cultured human mesa ngial cells. Methods. MCP-1 in serum or urine and urinary albumin (Alb) as well as sever al clinical parameters such as plasma glucose, serum Gly-Alb, and hemoglobi n Alc (HbA1c) were measured after overnight fasting in 16 control subjects and 54 diabetic patients. The relationships between the levels of urinary A lb and urinary or serum MCP-1 and also between the values of respective cli nical parameter and urinary MCP-1 levels were analyzed. Next, using culture d human mesangial cells, we investigated the role of Gly-Alb and/or HG on t he gene and protein expression of MCP-1. Results. Urinary levels (ng/g creatinine), but not serum levels, of MCP-1 i ncreased in accordance with the extent of albuminuria. In all subjects, the re were significant correlations between the urinary levels of Alb and MCP- 1 (r = 0.746, P < 0.0001) and between the levels of serum Gly-Alb and urina ry MCP-1 (r = 0.475, P < 0.0001). In cultured human mesangial cells, the ge ne and protein expression of MCP-1 was dose and time dependently up-regulat ed by Gly-Alb. HG slightly but significantly stimulated MCP-1 expression. T he combination of Gly-Alb and HG showed the greatest stimulation in more th an an additive manner on MCP-1 production. Conclusions. This study suggests that facilitated MCP-1 production by mesan gial cells in diabetic milieu contributes to the initiation and progression of diabetic nephropathy.