title: Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: First Department of Internal Medicine and Division of Blood Purification, School of Medicine, and Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. twada@medf.m.knazawa-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Furuichi
authors.forename: N
authors.initials: N
authors.lastname: Sakai
authors.forename: Y
authors.initials: Y
authors.lastname: Iwata
authors.forename: K
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: S I
authors.initials: SI
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Takasawa
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.forename: H
authors.initials: H
authors.lastname: Kida
authors.forename: K I
authors.initials: KI
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Mukaida
authors.forename: T
authors.initials: T
authors.lastname: Naito
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002465:Cell Movement / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics* / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta