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- Title
Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy.
- Authors
Banba, Nobuyuki; Nakamura, Tsutomu; Matsumura, Michiko; Kuroda, Hisamoto; Hattori, Yoshiyuki; Kasai, Kikuo; Banba, N; Nakamura, T; Matsumura, M; Kuroda, H; Hattori, Y; Kasai, K
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>This study suggests that facilitated MCP-1 production by mesangial cells in diabetic milieu contributes to the initiation and progression of diabetic nephropathy.
- Subjects
DIABETIC nephropathies; MONOCYTES
- Publication
Kidney International, 2000, Vol 58, Issue 2, p684
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1046/j.1523-1755.2000.00214.x