Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thickening of the tubular basement membrane is one of the hallmarks of the polycystic kidney disease (PKD). The present study was conducted to investigate the potential role of the matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitors (TIMP-1 and TIMP-2) in the accumulation of matrix components in PKD. As a model of PKD, two-month-old heterozygous Han:SPRD rats, which are at an early stage of cystogenesis, were used. MMP-2, but not MMP-9 (gelatinase B) nor MMP-3 (stromelysin) could be detected in proximal tubules of the normal rat kidney. The presence of the inhibitors TIMP-1 and TIMP-2 was confirmed on the mRNA level. In tubules from PKD rats MMP-2 activity was lower (31 +/- 8 vs. 58 +/- 7 U/prep., N = 9, P < 0.05), mRNA of MMP-2 was reduced 4.2 +/- 0.6-fold (N = 4, P < 0.05) and enzyme protein was depressed 3.8 +/- 0.8-fold (N = 4, P < 0.05). By contrast, TIMP-1 mRNA was 9.0 +/- 1.1-fold and TIMP-2 mRNA 3.8 +/- 0.7-fold (N = 4, P < 0.05) elevated over controls. Cyst fluid from homozygous rats contained MMP-2 protein and activity. These findings indicate that tubular MMP-2 activity is reduced in PKD, due to down-regulation of MMP-2, up-regulation of TIMP-1 and TIMP-2, and luminal secretion of the enzyme. It is conceivable that these alterations relate to the enhanced matrix accumulation observed in the evolution of PKD.
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PMID:Tubular gelatinase A (MMP-2) and its tissue inhibitors in polycystic kidney disease in the Han:SPRD rat. 877 Sep 51

It was previously found that elevated levels of matrix metalloproteinase (MMP)-2 (gelatinase A) and -9 (gelatinase B) were synthesized and secreted into the medium by cultured kidney tubules derived from cystic C57BL/6J-cpk mice. To determine whether increased synthesis and secretion occur in vivo in this mouse model of polycystic kidney disease, kidney protein extracts, mRNA, and tissue sections were compared for expression and activity of MMP-2 and -9. Although both MMP were detected in tissue extracts, the differences in expression levels and activity in normal and cystic kidneys were far greater for MMP-2. High levels of MMP-2 seemed to result from increased expression by the cystic kidneys predominantly in the second and third postnatal weeks (a time when the kidneys are undergoing rapid cystic enlargement). Much of the increased MMP was present in the inactive zymogen form, although active enzyme was readily detected by sodium dodecyl sulfate-polyacrylamide gel zymography and in situ zymography. MMP-2 was abnormally localized to the interstitium and to foci between cysts, suggesting that MMP-2 may regulate collagen accumulation at those sites, thus allowing cyst enlargement and limiting the severity of interstitial fibrosis.
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PMID:Matrix metalloproteinase-2 in a murine model of infantile-type polycystic kidney disease. 1021 19

Abdominal aortic aneurysm is well known to be associated with autosomal dominant polycystic kidney disease. Kidney tubules of autosomal dominant polycystic kidney disease synthesize and secrete high levels of matrix metalloproteinase 2, 3, and 9, especially matrix metalloproteinase 2, and serum matrix metalloproteinase 1 and plasma matrix metalloproteinase 9 concentrations in the disease are significantly higher than those in healthy controls. On the other hand, matrix metalloproteinases play a crucial role in the pathogenesis of abdominal aortic aneurysm. Inflammatory cell expression of matrix metalloproteinase 9 plays a critical role in an experimental model of aortic aneurysm disease. Macrophage-derived matrix metalloproteinase 9 and mesenchymal cell matrix metalloproteinase 2 are both required and work in concert to produce abdominal aortic aneurysm. The plasma matrix metalloproteinase 9 levels are significantly higher in the patients with abdominal aortic aneurysm than in the patients with aortoiliac occlusive disease or the healthy patients. Remarkably elevated matrix metalloproteinase 2 mRNA and protein levels in abdominal aortic aneurysm tissues as compared with normal and atherosclerotic aortic tissues are detected, and matrix metalloproteinase 2 proteolytic activity is several-fold higher in abdominal aortic aneurysms than in other pathological or normal states. Patients with abdominal aortic aneurysm elevate matrix metalloproteinase 2 levels in the vasculature remote from the aorta, supporting both the systemic nature of aneurysmal disease and a primary role of matrix metalloproteinase 2 in aneurysm formation. The authors propose a novel hypothesis that matrix metalloproteinases, synthesized and secreted by kidney tubules of autosomal dominant polycystic kidney disease, play a critical role in development of a concurrent abdominal aortic aneurysm.
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PMID:Matrix metalloproteinases synthesized in autosomal dominant polycystic kidney disease play a role in development of a concurrent abdominal aortic aneurysm. 1569 96