Extracellular matrix Degradation

Cl. Cajot, J. F., Schleuning, W. D., Medcalf, R. L., Bamat, J., Tetuz, J., Libermann, L., and Sordat, B., Mouse L-cells expressing human prourokinase-type plasminogen activator Effects on extracellular matrix degradation and invasion. J. Cell. Biol. 109, 915-925 (1989). 

To further extend the utility of structural methods, researchers compare solid state X-ray crystallographic and solution-state NMR structures to define important differences. For instance, the Bertini group has studied the enzyme matrix metalloproteinase 12 (MMP12), in the presence of its inhibitors. Matrix metalloproteinases (MMPs) are involved in extracellular matrix degradation, a fundamental step in tissue remodeling and repair. There are a great variety of enzymes of this type, the one studied here is one of many found in humans. Most MMPs have three domains (1) a prodomain that is removed... 

Several mechanisms can be proposed by which kallikreins can be involved in the pathogenesis of endocrine-related malignancies. Proteolytic enzymes are thought to be involved in tumor progression because of their role in extracellular matrix degradation. Many studies have shown that a variety of proteolytic enzymes are overproduced either by the cancer cells themselves or by the surrounding stromal cells, and that their overexpression is associated with unfavorable clinical prognosis [249],... 

Fujisawa T, Hattori T, Takahashi K, Kuboki T, Yamashita A, Takigawa, M. Cyclic mechanical stress induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin-1. J Biochem (Tokyo). 1999 125 966-975. 

Proteases contribute to the inflammatory response to injury, forming a final common pathway that leads to BBB breakdown, hemorrhage, and cell death. After traumatic and ischemic injuries, there is a buildup of lactate, which is increased with hyperglycemia. Acidosis leads to release of acid hydrolases, which are destructive enzymes that attack cellular components, including membranes, resulting in cell necrosis. In situations where the pH remains neutral, increases in intracellular calcium and cytokines cause induction of neutral proteases. The main neutral proteases are the extracellular matrix-degrading MMPs, plasminogen activator/plasmin, and caspases. 

The Boyden-chamber chemoinvasion sissay, developed by Albini et al. (1987) using Matrigel , is an alternative simplified model system for measuring cell capacity to attach to extracellular matrix, degrade it, and migrate towards a chemoattractant. Matrigel is a... 

Borchers, A. H., Sanders, L. A., Powell, M. B. and Bowden, G. T. (1997). Melanocyte mediated paracrine induction of extracellular matrix degrading proteases in squamous cell carcinoma cells. Exp. Cell Res. 231, til-65. 

Ribatti, D., Alessandri, G., Vacca, A., lurlaro, M. and Ponzoni, M. (1998). Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce endothelial cell proliferation and are angiogenic in vivo. Int. J. Cancer 77, 449-454. 

Growdi factor cytokine diat acts on monocytes and macrophages to cause them to differentiate Proteolytic enzyme diat can degrade components of die extracellular matrix Degradation product of activated C3 Degradation product of activated C4... 

Benyon R, Arthur M. Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 2001 21 373-84. 

Romanic, A. M. and Madri, J. A., Extracellular matrix-degrading proteinase in the nervous system, Brain Pathol., 4, 145, 1994. 

R. M. Senior and E. J. Campbell. Neutral proteases from human inflammatory cells. A critical review of their role in extracellular matrix degradation. Clin. Lab. Med. 3 645 (1983). 

Corticosteroids have antiangiogenic, antifibrotic, and antipermeability properties. The principle effects of steroids are stabilization of the blood-retinal barrier, resorption of exudation, and downregulation of inflammatory stimuli. Antiangiogenesis is a secondary effect felt to be mediated primarily by upregulation of extracellular matrix protein plasminogen activator inhibitor-1 (PAI-1) in vascular endothelial cells (18). This inhibits activation of plasmin and alters extracellular matrix degradation. 

Chondrocytes, the only cell type found in normal mature articular cartilage, are responsible for the maintenance and repair of this tissue, which happens to be the site of pathologic matrix remodeling and degradation in arthritis [51]. Indeed, chondrocyte apoptosis is a feature of osteoarthritic cartilage and is closely associated with extracellular matrix degradation. Fibrillated cartilage from osteoarthritic joints has been found to contain apoptotic cells in both the superficial and mid zones. In... 

Clark, E. S., Whigham, A. S., Yarbrough, W. G., and Weaver, A. M. (2007) Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Caneer Res. 67, 4227H235. 

M. A., Luini, A., and Buccione, R. (2003) Dynamin participates in focal extracellular matrix degradation by invasive cells. Mol. Biol. Cell. 14, 1074-1084. 

S. C. (2001) Invadopodia unique methods for measurement of extracellular matrix degradation in vitro. Methods Cell Biol. 63, 613-627. 

Metalloproteinases especially matrix metalloproteinases are a group of endopeptidases that contribute for the extracellular matrix degradation, and several tissue remodeling processes. Improper regulation of these endopeptidases could lead to several severe pathological problems that include cardiac, cartilage, and cancer-related diseases. Until now, many synthetic matrix metalloproteinase inhibitory substances (MMPIs) have been reported however, many of them could not make to the final clinical trials. 

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