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doi: 10.1242/10.1242/jcs.00063
Commentary |
1 BHF Blood Pressure Group, Department of Medicine and Therapeutics, Western
Infirmary, Glasgow G11 6NT, UK
2 School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ,
UK
* Present address: Department of Oncology, Cambridge University, Institute for
Medical Research, Hills Road, Cambridge CB2 2XY, UK
Author for correspondence (e-mail:
gm290{at}cam.ac.uk)
Tissue inhibitors of metalloproteinases (TIMPs) are the major cellular
inhibitors of the matrix metalloproteinase (MMP) sub-family, exhibiting
varying efficacy against different members, as well as different tissue
expression patterns and modes of regulation. Other proteins have modest
inhibitory activity against some of the MMPs, including domains of netrins,
the procollagen C-terminal proteinase enhancer (PCPE), the reversion-inducing
cysteine-rich protein with Kazal motifs (RECK), and tissue factor pathway
inhibitor (TFPI-2), but their physiological significance is not at all clear.
2-Macroglobulin, thrombospondin-1 and thrombospondin-2 can bind to some
MMPs and act as agents for their removal from the extracellular environment.
In contrast, few effective inhibitors of other members of the metzincin
family, the astacins or the distintegrin metalloproteinases, ADAMs have been
identified.
Many of these MMP inhibitors, including the TIMPs, possess other biological activities which may not be related to their inhibitory capacities. These need to be thoroughly characterized in order to allow informed development of MMP inhibitors as potential therapeutic agents. Over activity of MMPs has been implicated in many diseases, including those of the cardiovascular system, arthritis and cancer. The development of synthetic small molecule inhibitors has been actively pursued for some time, but the concept of the use of the natural inhibitors, such as the TIMPs, in gene based therapies is being assessed in animal models and should provide useful insights into the cell biology of degradative diseases.
Key words: MMP, TIMP, RECK, Therapy
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J. D. Lovelock, A. H. Baker, F. Gao, J.-F. Dong, A. L. Bergeron, W. McPheat, N. Sivasubramanian, and D. L. Mann Heterogeneous effects of tissue inhibitors of matrix metalloproteinases on cardiac fibroblasts Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H461 - H468. [Abstract] [Full Text] [PDF]
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M. P. Sanderson, S. N. Erickson, P. J. Gough, K. J. Garton, P. T. Wille, E. W. Raines, A. J. Dunbar, and P. J. Dempsey ADAM10 Mediates Ectodomain Shedding of the Betacellulin Precursor Activated by p-Aminophenylmercuric Acetate and Extracellular Calcium Influx J. Biol. Chem., January 21, 2005; 280(3): 1826 - 1837. [Abstract] [Full Text] [PDF]
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 A. K. Behera, E. Hildebrand, J. Scagliotti, A. C. Steere, and L. T. Hu Induction of Host Matrix Metalloproteinases by Borrelia burgdorferi Differs in Human and Murine Lyme Arthritis Infect. Immun., January 1, 2005; 73(1): 126 - 134. [Abstract] [Full Text] [PDF]
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 A. C. Newby Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture Physiol Rev, January 1, 2005; 85(1): 1 - 31. [Abstract] [Full Text] [PDF]
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E.-M. Schnaeker, R. Ossig, T. Ludwig, R. Dreier, H. Oberleithner, M. Wilhelmi, and S. W. Schneider Microtubule-Dependent Matrix Metalloproteinase-2/Matrix Metalloproteinase-9 Exocytosis: Prerequisite in Human Melanoma Cell Invasion Cancer Res., December 15, 2004; 64(24): 8924 - 8931. [Abstract] [Full Text] [PDF]
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J. Oh, D.-W. Seo, T. Diaz, B. Wei, Y. Ward, J. M. Ray, Y. Morioka, S. Shi, H. Kitayama, C. Takahashi, et al. Tissue Inhibitors of Metalloproteinase 2 Inhibits Endothelial Cell Migration through Increased Expression of RECK Cancer Res., December 15, 2004; 64(24): 9062 - 9069. [Abstract] [Full Text] [PDF]
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 S. Curran, S. R. Dundas, J. Buxton, M. F. Leeman, R. Ramsay, and G. I. Murray Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Phenotype Identifies Poor Prognosis Colorectal Cancers Clin. Cancer Res., December 15, 2004; 10(24): 8229 - 8234. [Abstract] [Full Text] [PDF]
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H. Toft-Hansen, R. K. Nuttall, D. R. Edwards, and T. Owens Key Metalloproteinases Are Expressed by Specific Cell Types in Experimental Autoimmune Encephalomyelitis J. Immunol., October 15, 2004; 173(8): 5209 - 5218. [Abstract] [Full Text] [PDF]
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C. Van Themsche, T. Alain, A. E. Kossakowska, S. Urbanski, E. F. Potworowski, and Y. St-Pierre Stromelysin-2 (Matrix Metalloproteinase 10) Is Inducible in Lymphoma Cells and Accelerates the Growth of Lymphoid Tumors In Vivo J. Immunol., September 15, 2004; 173(6): 3605 - 3611. [Abstract] [Full Text] [PDF]
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H. G. Munshi, Y. I. Wu, S. Mukhopadhyay, A. J. Ottaviano, A. Sassano, J. E. Koblinski, L. C. Platanias, and M. S. Stack Differential Regulation of Membrane Type 1-Matrix Metalloproteinase Activity by ERK 1/2- and p38 MAPK-modulated Tissue Inhibitor of Metalloproteinases 2 Expression Controls Transforming Growth Factor-{beta}1-induced Pericellular Collagenolysis J. Biol. Chem., September 10, 2004; 279(37): 39042 - 39050. [Abstract] [Full Text] [PDF]
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A. R. Walmsley, G. McCombie, U. Neumann, D. Marcellin, R. Hillenbrand, A. K. Mir, and S. Frentzel Zinc metalloproteinase-mediated cleavage of the human Nogo-66 receptor J. Cell Sci., September 1, 2004; 117(19): 4591 - 4602. [Abstract] [Full Text] [PDF]
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M.-H. Lee and G. Murphy Matrix metalloproteinases at a glance J. Cell Sci., August 15, 2004; 117(18): 4015 - 4016. [Full Text] [PDF]
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O. Salvucci, M. Basik, L. Yao, R. Bianchi, and G. Tosato Evidence for the involvement of SDF-1 and CXCR4 in the disruption of endothelial cell-branching morphogenesis and angiogenesis by TNF-{alpha} and IFN-{gamma} J. Leukoc. Biol., July 1, 2004; 76(1): 217 - 226. [Abstract] [Full Text] [PDF]
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 I. K. Y. Lo, L. L. Marchuk, R. Hollinshead, D. A. Hart, and C. B. Frank Matrix Metalloproteinase and Tissue Inhibitor of Matrix Metalloproteinase mRNA Levels Are Specifically Altered in Torn Rotator Cuff Tendons Am. J. Sports Med., July 1, 2004; 32(5): 1223 - 1229. [Abstract] [Full Text] [PDF]
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X. Shi-wen, S. L. Howat, E. A. Renzoni, A. Holmes, J. D. Pearson, M. R. Dashwood, G. Bou-Gharios, C. P. Denton, R. M. du Bois, C. M. Black, et al. Endothelin-1 Induces Expression of Matrix-associated Genes in Lung Fibroblasts through MEK/ERK J. Biol. Chem., May 28, 2004; 279(22): 23098 - 23103. [Abstract] [Full Text] [PDF]
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N. E. Sounni, C. Roghi, V. Chabottaux, M. Janssen, C. Munaut, E. Maquoi, B. G. Galvez, C. Gilles, F. Frankenne, G. Murphy, et al. Up-regulation of Vascular Endothelial Growth Factor-A by Active Membrane-type 1 Matrix Metalloproteinase through Activation of Src-Tyrosine Kinases J. Biol. Chem., April 2, 2004; 279(14): 13564 - 13574. [Abstract] [Full Text] [PDF]
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J. Zou, F. Zhu, J. Liu, W. Wang, R. Zhang, C. G. Garlisi, Y.-H. Liu, S. Wang, H. Shah, Y. Wan, et al. Catalytic Activity of Human ADAM33 J. Biol. Chem., March 12, 2004; 279(11): 9818 - 9830. [Abstract] [Full Text] [PDF]
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H. Nakamura, N. Suenaga, K. Taniwaki, H. Matsuki, K. Yonezawa, M. Fujii, Y. Okada, and M. Seiki Constitutive and Induced CD44 Shedding by ADAM-Like Proteases and Membrane-Type 1 Matrix Metalloproteinase Cancer Res., February 1, 2004; 64(3): 876 - 882. [Abstract] [Full Text] [PDF]
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 Y. S. Kanwar, J. Wada, S. Lin, F. R. Danesh, S. S. Chugh, Q. Yang, T. Banerjee, and J. W. Lomasney Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis Am J Physiol Renal Physiol, February 1, 2004; 286(2): F202 - F215. [Abstract] [Full Text] [PDF]
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E. L. Martin, B. Z. Moyer, M. C. Pape, B. Starcher, K. J. Leco, and R. A. W. Veldhuizen Negative impact of tissue inhibitor of metalloproteinase-3 null mutation on lung structure and function in response to sepsis Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1222 - L1232. [Abstract] [Full Text] [PDF]
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C. A. Fernandez, C. Butterfield, G. Jackson, and M. A. Moses Structural and Functional Uncoupling of the Enzymatic and Angiogenic Inhibitory Activities of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2): LOOP 6 IS A NOVEL ANGIOGENESIS INHIBITOR J. Biol. Chem., October 17, 2003; 278(42): 40989 - 40995. [Abstract] [Full Text] [PDF]
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M.-H. Lee, M. Rapti, and G. Murphy Unveiling the Surface Epitopes That Render Tissue Inhibitor of Metalloproteinase-1 Inactive against Membrane Type 1-Matrix Metalloproteinase J. Biol. Chem., October 10, 2003; 278(41): 40224 - 40230. [Abstract] [Full Text] [PDF]
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S. Mitola, M. Strasly, M. Prato, P. Ghia, and F. Bussolino IL-12 Regulates an Endothelial Cell-Lymphocyte Network: Effect on Metalloproteinase-9 Production J. Immunol., October 1, 2003; 171(7): 3725 - 3733. [Abstract] [Full Text] [PDF]
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A. Remacle, G. Murphy, and C. Roghi Membrane type I-matrix metalloproteinase (MT1-MMP) is internalised by two different pathways and is recycled to the cell surface J. Cell Sci., October 1, 2003; 116(19): 3905 - 3916. [Abstract] [Full Text] [PDF]
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B. S. Wiseman, M. D. Sternlicht, L. R. Lund, C. M. Alexander, J. Mott, M. J. Bissell, P. Soloway, S. Itohara, and Z. Werb Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis J. Cell Biol., September 15, 2003; 162(6): 1123 - 1133. [Abstract] [Full Text] [PDF]
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R. Visse and H. Nagase Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases: Structure, Function, and Biochemistry Circ. Res., May 2, 2003; 92(8): 827 - 839. [Abstract] [Full Text] [PDF]
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M.-C. Hall, D. A. Young, J. G. Waters, A. D. Rowan, A. Chantry, D. R. Edwards, and I. M. Clark The Comparative Role of Activator Protein 1 and Smad Factors in the Regulation of Timp-1 and MMP-1 Gene Expression by Transforming Growth Factor-beta 1 J. Biol. Chem., March 14, 2003; 278(12): 10304 - 10313. [Abstract] [Full Text] [PDF]
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A. Castrillo, S. B. Joseph, C. Marathe, D. J. Mangelsdorf, and P. Tontonoz Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages J. Biol. Chem., March 14, 2003; 278(12): 10443 - 10449. [Abstract] [Full Text] [PDF]
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 R. K. Nuttall, C. J. Pennington, J. Taplin, A. Wheal, V. W. Yong, P. A. Forsyth, and D. R. Edwards Elevated Membrane-Type Matrix Metalloproteinases in Gliomas Revealed by Profiling Proteases and Inhibitors in Human Cancer Cells Mol. Cancer Res., March 1, 2003; 1(5): 333 - 345. [Abstract] [Full Text] [PDF]
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