Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy.
BACKGROUND
Monocyte chemoattractant protein-1 (MCP-1) is a specific chemokine to recruit and activate monocytes from the circulation to inflammatory site. In diabetic nephropathy, similar to other glomerulonephropathies, infiltration and activation of monocytes/macrophages in glomerulus have been implicated in the development of glomerular injury. The aim of the present study was to examine a possible relationship of MCP-1 with diabetic nephropathy and to investigate the role of glycated albumin (Gly-Alb) as well as high concentration of glucose (HG) on MCP-1 production by cultured human mesangial cells.


METHODS
MCP-1 in serum or urine and urinary albumin (Alb) as well as several clinical parameters such as plasma glucose, serum Gly-Alb, and hemoglobin A1c (HbA1c) were measured after overnight fasting in 16 control subjects and 54 diabetic patients. The relationships between the levels of urinary Alb and urinary or serum MCP-1 and also between the values of respective clinical parameter and urinary MCP-1 levels were analyzed. Next, using cultured human mesangial cells, we investigated the role of Gly-Alb and/or HG on the gene and protein expression of MCP-1.


RESULTS
Urinary levels (ng/g creatinine), but not serum levels, of MCP-1 increased in accordance with the extent of albuminuria. In all subjects, there 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 urinary MCP-1 (r = 0.475, P < 0.0001). In cultured human mesangial cells, the gene and protein expression of MCP-1 was dose and time dependently up-regulated by Gly-Alb. HG slightly but significantly stimulated MCP-1 expression. The combination of Gly-Alb and HG showed the greatest stimulation in more than an additive manner on MCP-1 production.


CONCLUSIONS
This study suggests that facilitated MCP-1 production by mesangial cells in diabetic milieu contributes to the initiation and progression of diabetic nephropathy.
Banba
N
N
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Tochigi, Japan.
Nakamura
T
T
Matsumura
M
M
Kuroda
H
H
Hattori
Y
Y
Kasai
K
K
D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000276:immunology / Q000652:urine; D001786:Blood Glucose; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000276:immunology* / Q000652:urine; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology; D017127:Glycation End Products, Advanced; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000276:immunology / Q000652:urine; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin; D000093423:Glycated Serum Albumin
D001786:Blood Glucose; D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D000093423:Glycated Serum Albumin