Matrix metalloproteinase-2 (MMP-2) and membrane-type 1 MMP (MT1-MMP) affect the remodeling of glomerulosclerosis in diabetic OLETF rats.
Nephrol Dial Transplant
; 26(10): 3124-31, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21414971
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.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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinase 2 da Matriz
/
Complicações do Diabetes
/
Diabetes Mellitus Tipo 2
/
Nefropatias Diabéticas
/
Metaloproteinase 14 da Matriz
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article