Matrix metalloproteinase-2 (MMP-2) and membrane-type 1 MMP (MT1-MMP) affect the remodeling of glomerulosclerosis in diabetic OLETF rats

Nephrol Dial Transplant. 2011 Oct;26(10):3124-31. doi: 10.1093/ndt/gfr125. Epub 2011 Mar 17.


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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria
  • Animals
  • Blotting, Western
  • Diabetes Complications / etiology
  • Diabetes Complications / metabolism*
  • Diabetes Complications / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Immunoenzyme Techniques
  • Male
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Monocrotaline / toxicity
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred OLETF
  • Real-Time Polymerase Chain Reaction


  • RNA, Messenger
  • Monocrotaline
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14