title: Matrix metalloproteinase-2 (MMP-2) and membrane-type 1 MMP (MT1-MMP) affect the remodeling of glomerulosclerosis in diabetic OLETF rats.
abstract: BACKGROUND
  We reported previously that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. However, the precise mechanism has yet to be elucidated. Here, we investigated the roles of matrix metalloproteinase (MMP)-2, which is activated from proMMP-2 by membrane-type (MT)-MMP in the sclerotic and endothelial cell injury process of a type II diabetic model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
  
  
  METHODS
  Monocrotaline (MCT) or saline only was injected three times every 4 weeks in 36-week-old OLETF rats and control Long-Evans Tokushima Otsuka rats. Glomerular expression and enzymatic activity of MMP-2 and MT1-MMP were assessed by immunohistochemistry, gelatin zymography of cultured glomerular supernatants, in situ enzymatic detection and reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Mesangial matrix increased in OLETF rats. In addition, mesangiolysis and nodular-like mesangial expansion were observed only in MCT-injected endothelial injured OLETF rats. MMP-2 and MT1-MMP proteins increased in the expanded mesangial lesions in OLETF rats. Gelatin zymography revealed an increase in 62-kDa activated MMP-2 in the culture supernatants of isolated glomeruli from OLETF rats. In situ enzymatic activity of MMP in the mesangial areas was also detected in 50-week-old MCT-injected OLETF rats.
  
  
  CONCLUSIONS
  These results suggest that MMP-2 and MT1-MMP are produced and activated in glomeruli through the progression of diabetic nephropathy and may have some effect on the remodeling of the glomerular matrix in diabetic nephropathy.
authors.affiliation: Division of Blood Purification, Kanazawa University Hospital, Kanazawa Japan. kfuruichi@m-kanazawa.jp
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Hisada
authors.forename: Miho
authors.initials: M
authors.lastname: Shimizu
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okumura
authors.forename: Kiyoki
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
mesh_terms: D000419:Albuminuria; D000818:Animals; D015153:Blotting, Western; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D016686:Monocrotaline / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020334:Rats, Inbred OLETF; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D016686:Monocrotaline; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14