Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy

Kidney Int. 2000 Oct;58(4):1492-9. doi: 10.1046/j.1523-1755.2000.00311.x.


Background: We previously described that monocyte chemoattractant protein-1 (MCP-1) plays an important role in progressive glomerular and interstitial damage in inflammatory renal diseases. However, the expression of MCP-1 in diabetic nephropathy remains to be investigated.

Methods: We examined whether locally expressed MCP-1 participates in human diabetic nephropathy via recruiting and activating monocytes/macrophages (Mphi). Urinary and serum MCP-1 levels were measured by enzyme-linked immunosorbent assay in 45 patients with diabetic nephropathy. The presence of MCP-1 in diseased kidneys was determined by immunohistochemical and in situ hybridization analyses.

Results: Urinary MCP-1 levels were significantly elevated in patients with diabetic nephrotic syndrome and advanced tubulointerstitial lesions. Moreover, urinary levels of MCP-1 were well correlated with the number of CD68-positive infiltrating cells in the interstitium. In contrast, serum MCP-1 levels remained similar to those of healthy volunteers. Furthermore, we detected the MCP-1-positive cells in the interstitium of diabetic nephropathy via both immunohistochemical and in situ hybridization analyses.

Conclusion: These observations suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy as well as inflammatory renal diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Movement / immunology
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / urine*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology*
  • Diabetic Nephropathies / urine
  • Female
  • Gene Expression / physiology
  • Humans
  • In Situ Hybridization
  • Macrophages / cytology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / metabolism
  • Nephritis, Interstitial / pathology
  • Nephritis, Interstitial / physiopathology*
  • Nephritis, Interstitial / urine
  • RNA, Messenger / analysis
  • Transcription, Genetic / physiology
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation / genetics


  • Chemokine CCL2
  • RNA, Messenger
  • Transforming Growth Factor beta