Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy

Kidney Int. 2000 Aug;58(2):684-90. doi: 10.1046/j.1523-1755.2000.00214.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / blood
  • Albuminuria / immunology
  • Albuminuria / urine
  • Blood Glucose
  • Cells, Cultured
  • Chemokine CCL2 / blood*
  • Chemokine CCL2 / metabolism
  • Chemokine CCL2 / urine*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / urine
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / immunology*
  • Diabetic Nephropathies / urine
  • Female
  • Glomerular Mesangium / cytology
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / immunology
  • Hyperglycemia / urine
  • Male
  • Middle Aged
  • Serum Albumin*

Substances

  • Blood Glucose
  • Chemokine CCL2
  • Serum Albumin
  • glycosylated serum albumin