The FASEB Journal, Vol 5, 2145-2154, Copyright © 1991 by The Federation of American Societies for Experimental Biology

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Matrix metalloproteinases and their inhibitors in connective tissue remodeling

JF Woessner Jr
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101.

Matrix metalloproteinases are an important group of zinc enzymes responsible for degradation of the extracellular matrix components such as collagen and proteoglycans in normal embryogenesis and remodeling and in many disease processes such as arthritis, cancer, periodontitis, and osteoporosis. A matrixin family is defined, comprising at least seven members that range in size from Mr 28,000 to 92,000 and are related in gene sequence to collagenase. All family members are secreted as zymogens that lose peptides of about 10,000 daltons upon activation. Latency is due to a conserved cysteine that binds to zinc at the active center. Latency is overcome by physical (chaotropic agents), chemical (HOCl, mercurials), and enzymatic (trypsin, plasmin) treatments that separate the cysteine residue from the zinc. Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP-1 binding site. A family of protein inhibitors of Mr 28,500 or less binds strongly and stoichiometrically in noncovalent fashion to inhibit members of the family. The serum protein alpha 2-macroglobulin and relatives are also strongly inhibitory.

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				G. M. Liuzzi, T. Latronico, A. Fasano, G. Carlone, and P. Riccio Interferon-beta inhibits the expression of metalloproteinases in rat glial cell cultures: implications for multiple sclerosis pathogenesis and treatment Multiple Sclerosis, June 1, 2004; 10(3): 290 - 297. [Abstract] [PDF]

				M. Delgado, D. Pozo, and D. Ganea The Significance of Vasoactive Intestinal Peptide in Immunomodulation Pharmacol. Rev., June 1, 2004; 56(2): 249 - 290. [Abstract] [Full Text] [PDF]

				A. L. Alderton, W. J. Means, N. Kalchayanand, R. J. McCormick, and K. W. Miller Bovine metalloprotease characterization and in vitro connective tissue degradation J Anim Sci, May 1, 2004; 82(5): 1475 - 1481. [Abstract] [Full Text] [PDF]

				F.-C. Ke, L.-C. Chuang, M.-T. Lee, Y. J. Chen, S.-W. Lin, P. S. Wang, D. M. Stocco, and J.-J. Hwang The Modulatory Role of Transforming Growth Factor {beta}1 and Androstenedione on Follicle-Stimulating Hormone-Induced Gelatinase Secretion and Steroidogenesis in Rat Granulosa Cells Biol Reprod, May 1, 2004; 70(5): 1292 - 1298. [Abstract] [Full Text] [PDF]

				F. Cipollone, M. Fazia, A. Iezzi, B. Pini, C. Cuccurullo, M. Zucchelli, D. de Cesare, S. Ucchino, F. Spigonardo, M. De Luca, et al. Blockade of the Angiotensin II Type 1 Receptor Stabilizes Atherosclerotic Plaques in Humans by Inhibiting Prostaglandin E2-Dependent Matrix Metalloproteinase Activity Circulation, March 30, 2004; 109(12): 1482 - 1488. [Abstract] [Full Text] [PDF]

				C. I. Rodriguez, J.-G. Cheng, L. Liu, and C. L. Stewart Cochlin, a Secreted von Willebrand Factor Type A Domain-Containing Factor, Is Regulated by Leukemia Inhibitory Factor in the Uterus at the Time of Embryo Implantation Endocrinology, March 1, 2004; 145(3): 1410 - 1418. [Abstract] [Full Text] [PDF]

				K. W. Dwyer, P. P. Provenzano, P. Muir, W. B. Valhmu, and R. Vanderby Jr. Blockade of the sympathetic nervous system degrades ligament in a rat MCL model J Appl Physiol, February 1, 2004; 96(2): 711 - 718. [Abstract] [Full Text] [PDF]

				G. M. Liuzzi, C. M. Mastroianni, T. Latronico, F. Mengoni, A. Fasano, M. Lichtner, V. Vullo, and P. Riccio Anti-HIV drugs decrease the expression of matrix metalloproteinases in astrocytes and microglia Brain, February 1, 2004; 127(2): 398 - 407. [Abstract] [Full Text] [PDF]

				A. M. Tester, M. Waltham, S.-J. Oh, S.-N. Bae, M. M. Bills, E. C. Walker, F. G. Kern, W. G. Stetler-Stevenson, M. E. Lippman, and E. W. Thompson Pro-Matrix Metalloproteinase-2 Transfection Increases Orthotopic Primary Growth and Experimental Metastasis of MDA-MB-231 Human Breast Cancer Cells in Nude Mice Cancer Res., January 15, 2004; 64(2): 652 - 658. [Abstract] [Full Text] [PDF]

				R. E. Chapman and F. G. Spinale Extracellular protease activation and unraveling of the myocardial interstitium: critical steps toward clinical applications Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H1 - H10. [Full Text] [PDF]

				A. Huwiler, E.-S. Akool, A. Aschrafi, F. M. A. Hamada, J. Pfeilschifter, and W. Eberhardt ATP Potentiates Interleukin-1{beta}-induced MMP-9 Expression in Mesangial Cells via Recruitment of the ELAV Protein HuR J. Biol. Chem., December 19, 2003; 278(51): 51758 - 51769. [Abstract] [Full Text] [PDF]

				U. B. Hofmann, A. A. O. Eggert, K. Blass, E.-B. Brocker, and J. C. Becker Expression of Matrix Metalloproteinases in the Microenvironment of Spontaneous and Experimental Melanoma Metastases Reflects the Requirements for Tumor Formation Cancer Res., December 1, 2003; 63(23): 8221 - 8225. [Abstract] [Full Text] [PDF]

				N. M. Price, R. H. Gilman, J. Uddin, S. Recavarren, and J. S. Friedland Unopposed Matrix Metalloproteinase-9 Expression in Human Tuberculous Granuloma and the Role of TNF-{alpha}-Dependent Monocyte Networks J. Immunol., November 15, 2003; 171(10): 5579 - 5586. [Abstract] [Full Text] [PDF]

				H. Ida, S. A. Boylan, A. L. Weigel, and L. M. Hjelmeland Age-related changes in the transcriptional profile of mouse RPE/choroid Physiol Genomics, November 11, 2003; 15(3): 258 - 262. [Abstract] [Full Text] [PDF]

				C. D Liapis and K. I Paraskevas The pivotal role of matrix metalloproteinases in the development of human abdominal aortic aneurysms Vascular Medicine, November 1, 2003; 8(4): 267 - 271. [Abstract] [PDF]