Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury

2006 ◽  
Vol 20 (11) ◽  
pp. 1898-1900 ◽  
Author(s):  
Sunfa Cheng ◽  
Allan S. Pollock ◽  
Rajeev Mahimkar ◽  
Jean L. Olson ◽  
David H. Lovett ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Matrix Metalloproteinase ◽  
Renal Injury ◽  
Membrane Integrity ◽  
Matrix Metalloproteinase 2

scholarly journals Amelioration of neuropilin-1 and rage/matrix metalloproteinase-2 pathway-induced renal injury in diabetic rats by rosuvastatin

2021 ◽  
pp. 21-21
Author(s):  
Rabia Nabi ◽  
Sultan Alvi ◽  
Sultan Alouffi ◽  
Saif Khan ◽  
Adnan Ahmad ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Renal Injury ◽  
Reductase Activity ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Paraoxonase 1 ◽  
Matrix Metalloproteinase 2 ◽  
Altered Level ◽  
Neuropilin 1 ◽  
Coa Reductase

Advanced glycation end-products (AGEs) induce the production of reactive oxygen species (ROS) and extra cellular matrix (ECM) degradation via suppression of neuropilin-1 (NRP-1) and interaction with AGE-receptors (RAGE). This study aimed to reveal whether modulation of NRP-1 by rosuvastatin (RT) prevents AGE-induced renal injury via targeting RAGE/matrix metalloproteinase-2 (MMP-2) signaling in diabetic rats. Treatment with RT ameliorated the altered level of markers of glycemic control, renal injury, cholesterol, triglyceride (TG) and hepatic HMG-CoA reductase activity; the level of circulatory carboxymethyl-lysine (CML) and the accumulation of fluorogenic-AGEs in renal tissue was reduced; the expression of renal NRP-1, a checkpoint target, was stimulated; the transcription of RAGE, NF?B-2, TGF-?1 and MMP-2 was suppressed; the circulatory carbonyl content (CC) and paraoxonase-1 (PON-1) activity was ameliorated, and renal histopathological features were attenuated as evidenced by improved glomerular appearance, Bowman?s space and abundant podocytes in kidneys. In conclusion, RT exhibited the potential to counteract diabetes and AGE-induced renal pathologies via stimulation of NRP-1, suppression of RAGE, and of genes responsible for ECM disintegration (MMP-2) and the inflammatory response (NF?B-2).

Alveolar epithelial cells in vitro produce gelatinases and tissue inhibitor of matrix metalloproteinase-2

1997 ◽  
Vol 273 (3) ◽  
pp. L663-L675 ◽  
Author(s):  
M. P. d'Ortho ◽  
C. Clerici ◽  
P. M. Yao ◽  
C. Delacourt ◽  
C. Delclaux ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Matrix Metalloproteinase ◽  
Primary Cultures ◽  
Basement Membranes ◽  
Alveolar Epithelial Cells ◽  
Matrix Metalloproteinase 2 ◽  
Type Ii ◽  
Matrix Metalloproteinase 1 ◽  
Type Ii Pneumocytes

Type II pneumocytes are key cells of the alveolar epithelium. They lie on the alveolar basement membrane, which influences their phenotype and functions. We hypothesized that type II pneumocytes degrade basement membrane components by producing gelatinases, members of the matrix metalloproteinase family. To investigate this hypothesis, we used primary cultures of rat type II pneumocytes and cultures of the human A549 cell line. We found by zymography that 70-kDa gelatinase was present in media conditioned by these cells. This 70-kDa gelatinase was identified as gelatinase A by a Western blot, and the presence of its mRNA was demonstrated by reverse transcription-polymerase chain reaction. A 95-kDa gelatinase could be induced under certain conditions. Production of gelatinases may take place during the turnover of basement membranes, in physiological and in pathophysiological processes. This was suggested by the increase in production of both gelatinases that we observed after in vitro exposure to LPS or interleukin-1. The presence of tissue inhibitors of matrix metalloproteinase-1 and -2 was also demonstrated, suggesting that degradation of extracellular matrix by type II pneumocytes is tightly regulated.

Abstract 55: Involvement of Matrix Metalloproteinase-2 During the Progression of Renal Disease in Diabetic Dahl Salt-sensitive Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Tiffani Slaughter ◽  
Adrienne Paige ◽  
Fan Fan ◽  
Patrick Kyle ◽  
Aron M Geurts ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Matrix Metalloproteinase ◽  
Renal Disease ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Type I Diabetes ◽  
Matrix Metalloproteinase 2 ◽  
Type I ◽  
Protein Excretion ◽  
Low Salt

Recently, our laboratory reported that Dahl salt-sensitive (SS) rats develop a form of renal disease following induction of diabetes with streptozotocin (STZ) that is similar to patients with diabetic nephropathy (DN). The progression of renal injury in this model was associated with increased levels of matrix metalloproteinase-2 (MMP-2) in the renal cortex. The present study examined the role of MMP-2 during the progression of diabetes-induced renal injury by comparing the development of proteinuria and renal injury following the induction of type I diabetes in SS rats and in a MMP-2 Zinc finger KO strain of SS rats with an 8 base pair frame-shift deletion (1433-1440) in exon 7 (MMP-2 ZN KO strain). The glomerular expression of MMP-2 protein was non-detectable in the MMP-2 ZN KO strain compared to SS rats fed a low salt (LS) diet. We next performed studies using 9 week-old SS and MMP-2 ZN KO rats treated with either vehicle or (2) STZ, 50 mg/kg (i.p.) to induce diabetes and fed the rats a low salt (LS) diet containing 0.4% NaCl to minimize the development of hypertension. At 18 weeks of age, protein excretion increased to 303±39 mg/day in STZ-treated SS rats (n=7) versus 112±12 mg/day in vehicle treated rats. Protein excretion only increased to 150±23 mg/day in the STZ-treated MMP-2 ZN KO strain (n=7). Blood pressure was not significantly altered and averaged 109±4 mmHg in vehicle and STZ-treated SS rats versus 108±4 mmHg in the STZ-treated MMP2-ZN KO animals. STZ-treated SS rats exhibited marked glomerular injury and extensive renal fibrosis. The degree of glomerulosclerosis and renal interstitial fibrosis was significantly reduced in the kidneys of the MMP-2 ZN KO strain. These data indicate that the progression of diabetes-induced renal injury in STZ-SS rats is associated with upregulation of the expression and activity of MMP-2 and that KO of MMP-2 gene function markedly reduces the development of proteinuria and renal injury in this model of type I diabetic nephropathy. These results also suggest that selective MMP inhibitors may be useful to prevent the development and/or progression of chronic kidney disease in the millions of patients suffering from diabetes.

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