Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases (original) (raw)

• Barrett, A. J., Rawlings, N. D. & Woessner J. F. Handbook of Proteolytic Enzymes (Academic Press, London, 2004).
  Google Scholar
• Egeblad, M. & Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nature Rev. Cancer 2, 161–174 (2002).
  CAS Google Scholar
• Kobayashi, Y., Matsumoto, M., Kotani, M. & Makino, T. Possible involvement of matrix metalloproteinase-9 in Langerhans cell migration and maturation. J. Immunol. 163, 5989–5993 (1999).
  CAS PubMed Google Scholar
• Coussens, L. M., Fingleton, B. & Matrisian, L. M. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295, 2387–2392 (2002).
  Article CAS PubMed Google Scholar
• Overall, C. M. & Lopez-Otin, C. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nature Rev. Cancer 2, 657–672 (2002).
  CAS Google Scholar
• Van Wart, H. E. & Birkedal-Hansen, H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc. Natl Acad. Sci. USA 87, 5578–5582 (1990).
  CAS PubMed PubMed Central Google Scholar
• Kleifeld, O. et al. Structural characterization of the catalytic active site in the latent and active natural gelatinase B from human neutrophils. J. Biol. Chem. 275, 34335–34343 (2000).
  CAS PubMed Google Scholar
• Van den Steen, P. E. et al. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit. Rev. Biochem. Mol. Biol. 37, 375–536 (2002).
  CAS PubMed Google Scholar
• Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002). An excellent review on the similarities of the molecular processes between inflammation and cancer.
  Article CAS PubMed PubMed Central Google Scholar
• Creighton, C. & Hanash, S. Expression of matrix metalloproteinase 9 (MMP-9/gelatinase B) in adenocarcinomas strongly correlated with expression of immune response genes. In Silico Biol. 3, 301–311 (2003).
  CAS PubMed Google Scholar
• Opdenakker, G. & Van Damme, J. Cytokines and proteases in invasive processes: molecular similarities between inflammation and cancer. Cytokine 4, 251–258 (1992).
  CAS PubMed Google Scholar
• Opdenakker, G. & Van Damme, J. The countercurrent principle in invasion and metastasis of cancer cells. Recent insights on the roles of chemokines. Int. J. Dev. Biol. 48, 519–527 (2004).
  CAS PubMed Google Scholar
• Heissig, B. et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109, 625–637 (2002).
  CAS PubMed PubMed Central Google Scholar
• Chantrain, C. F. et al. Stromal matrix metalloproteinase-9 regulates the vascular architecture in neuroblastoma by promoting pericyte recruitment. Cancer Res. 64, 1675–1686 (2004).
  CAS PubMed Google Scholar
• Cuzner, M. L. and Opdenakker, G. Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system. J. Neuroimmunol. 94, 1–14 (1999).
  CAS PubMed Google Scholar
• Pruijt, J. F. M. et al. Prevention of interleukin-8-induced mobilization of hematopoietic progenitor cells in rhesus monkeys by inhibitory antibodies against the metalloproteinase gelatinase B (MMP-9). Proc. Natl Acad. Sci. USA 96, 10863–10868 (1999).
  CAS PubMed PubMed Central Google Scholar
• Opdenakker, G., Fibbe, W. E. & Van Damme, J. The molecular basis of leukocytosis. Immunol. Today 19, 182–189 (1998).
  CAS PubMed Google Scholar
• Kollet, O. et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nature Med. 12, 657–664 (2006).
  CAS PubMed Google Scholar
• Parks, W. C., Wilson, C. L. & Lopez-Boado, Y. S. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nature Rev. Immunol. 4, 617–629 (2004).
  CAS Google Scholar
• Van den Steen, P. E., Proost, P., Wuyts, A., Van Damme, J. & Opdenakker, G. Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-α and leaves RANTES and MCP-2 intact. Blood 96, 2673–2681 (2000). Together with references 21–23, 67 and 157, describes important regulatory effects of MMPs on chemokine and cytokine functions.
  CAS PubMed Google Scholar
• Van den Steen, P. E. et al. Gelatinase B/MMP-9 and neutrophil collagenase/MMP-8 process the chemokines human GCP-2/CXCL6, ENA-78/CXCL5 and mouse GCP-2/LIX and modulate their physiological activities. Eur. J. Biochem. 270, 3739–3749 (2003).
  CAS PubMed Google Scholar
• McQuibban, G. A. et al. Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289, 1202–1206 (2000).
  CAS PubMed Google Scholar
• McQuibban, G. A. et al. Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100, 1160–1167 (2002).
  CAS PubMed Google Scholar
• Whittaker, M., Floyd, C. D., Brown, P. & Gearing, A. J. Design and therapeutic application of matrix metalloproteinase inhibitors. Chem. Rev. 99, 2735–2776 (1999).
  CAS PubMed Google Scholar
• Hu, J., Van den Steen, P. E., Houde, M., Ilenchuk, T. T. & Opdenakker, G. Inhibitors of gelatinase B/matrix metalloproteinase-9 activity comparison of a peptidomimetic and polyhistidine with single-chain derivatives of a neutralizing monoclonal antibody. Biochem. Pharmacol. 67, 1001–1009 (2004).
  CAS PubMed Google Scholar
• Martens, E. et al. A monoclonal antibody inhibits gelatinase B/MMP-9 by selective binding to part of the catalytic domain and not to the fibronectin or zinc binding domains. Biochim. Biophys. Acta 1770, 178–186 (2007).
  CAS PubMed Google Scholar
• Chirco, R., Liu, X. W., Jung, K. K. & Kim, H. R. Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev. 25, 99–113 (2006).
  CAS PubMed Google Scholar
• Overall, C. M. & Kleifeld, O. Tumour microenvironment — opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nature Rev. Cancer 6, 227–239 (2006).
  CAS Google Scholar
• Kontogiorgis, C. A., Papaioannou, P. & Hadjipavlou-Litina, D. J. Matrix metalloproteinase inhibitors: a review on pharmacophore mapping and (Q)SARs results. Curr. Med. Chem. 12, 339–355 (2005).
  CAS PubMed Google Scholar
• Sang, Q. X. et al. Matrix metalloproteinase inhibitors as prospective agents for the prevention and treatment of cardiovascular and neoplastic diseases. Curr. Top. Med. Chem. 6, 289–316 (2006). Together with references 24 and 29, constitutes an excellent update on the medicinal chemistry of MMPIs.
  CAS PubMed Google Scholar
• Breuer, E., Frant, J. & Reich, R. Recent non-hydroxamate matrix metalloproteinase inhibitors. Expert Opin. Ther. Patents 15, 253–269 (2005).
  CAS Google Scholar
• Babine, R. E. & Bender, S. L. Molecular recognition of protein–ligand complexes: applications to drug design. Chem. Rev. 97, 1359–1472 (1997).
  CAS PubMed Google Scholar
• Maskos, K. Crystal structures of MMPs in complex with physiological and pharmacological inhibitors. Biochimie 87, 249–263 (2005).
  CAS PubMed Google Scholar
• Morgunova, E. et al. Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed. Science 284, 1667–1670 (1999).
  CAS PubMed Google Scholar
• Clements, J. M. et al. Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-α inhibitor. J. Neuroimmunol. 74, 85–94 (1997).
  CAS PubMed Google Scholar
• Xue, C. B. et al. Design and synthesis of cyclic inhibitors of matrix metalloproteinases and TNF-α production. J. Med. Chem. 41, 1745–1748 (1998).
  CAS PubMed Google Scholar
• Hu, J., Fiten, P., Van den Steen, P. E., Chaltin, P. & Opdenakker, G. Simulation of evolution-selected propeptide by high-throughput selection of a peptidomimetic inhibitor on a capillary DNA sequencer platform. Anal. Chem. 77, 2116–2124 (2005).
  CAS PubMed Google Scholar
• MacPherson, L. J. et al. Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits. J. Med. Chem. 40, 2525–2532 (1997).
  CAS PubMed Google Scholar
• Pikul, S. et al. Design and synthesis of phosphinamide-based hydroxamic acids as inhibitors of matrix metalloproteinases. J. Med. Chem. 42, 87–94 (1999).
  CAS PubMed Google Scholar
• Hamada, T., Arima, N., Shindo, M., Sugama, K. & Sasaguri, Y. Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase-inhibitor. Br. J. Pharmacol. 131, 1513–1520 (2000).
  CAS PubMed PubMed Central Google Scholar
• Gatto, C. et al. BAY 12–9566, a novel inhibitor of matrix metalloproteinases with antiangiogenic activity. Clin. Cancer Res. 5, 3603–3607 (1999).
  CAS PubMed Google Scholar
• Levin, J. I. et al. The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases. Bioorg. Med. Chem. Lett. 8, 1163–1168 (1998).
  CAS PubMed Google Scholar
• Wang, X., Choe, Y., Craik, C. S. & Ellman, J. A. Design and synthesis of novel inhibitors of gelatinase B. Bioorg. Med. Chem. Lett. 12, 2201–2204 (2002).
  CAS PubMed Google Scholar
• Brown, S. et al. Potent and selective mechanism-based inhibition of gelatinases. J. Am. Chem. Soc. 122, 6799–6800 (2000).
  CAS Google Scholar
• Kleifeld, O. et al. X-ray absorption studies of human matrix metalloproteinase-2 (MMP-2) bound to a highly selective mechanism-based inhibitor. Comparison with the latent and active forms of the enzyme. J. Biol. Chem. 276, 17125–17131 (2001).
  CAS PubMed Google Scholar
• Ikejiri, M. et al. Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A. J. Org. Chem. 70, 5709–5712 (2005).
  CAS PubMed Google Scholar
• Ferry, G., Boutin, J. A., Atassi, G., Fauchere, J. L. & Tucker, G. C. Selection of a histidine-containing inhibitor of gelatinases through deconvolution of combinatorial tetrapeptide libraries. Mol. Divers. 2, 135–146 (1997).
  CAS PubMed Google Scholar
• Koivunen, E. et al. Tumor targeting with a selective gelatinase inhibitor. Nature Biotech. 17, 768–774 (1999).
  CAS Google Scholar
• Acharya, M. R., Venitz, J., Figg, W. D. & Sparreboom, A. Chemically modified tetracyclines as inhibitors of matrix metalloproteinases. Drug Resist. Updat. 7, 195–208 (2004).
  PubMed Google Scholar
• Paemen, L. et al. The gelatinase inhibitory activity of tetracyclines and chemically modified tetracycline analogues as measured by a novel microtiter assay for inhibitors. Biochem. Pharmacol. 52, 105–111 (1996). The first study on the relation of structure and function of tetracyclines and CMTs as MMPIs.
  CAS PubMed Google Scholar
• Yrjanheikki, J. et al. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc. Natl Acad. Sci. USA 96, 13496–13500 (1999).
  CAS PubMed PubMed Central Google Scholar
• Yong, V. W., Power, C., Forsyth, P. & Edwards, D. R. Metalloproteinases in biology and pathology of the nervous system. Nature Rev. Neurosci. 2, 502–511 (2001).
  CAS Google Scholar
• Cohen, J. The immunopathogenesis of sepsis. Nature 420, 885–891 (2002).
  CAS PubMed Google Scholar
• Hotchkiss, R. S. & Karl, I. E. The pathophysiology and treatment of sepsis. N. Engl. J. Med. 348, 138–150 (2003).
  CAS PubMed Google Scholar
• Beutler, B. Toll-like receptors: how they work and what they do. Curr. Opin. Hematol. 9, 2–10 (2002).
  PubMed Google Scholar
• Dubois, B. et al. Gelatinase B deficiency protects against endotoxin shock. Eur. J. Immunol. 32, 2163–2171 (2002).
  CAS PubMed Google Scholar
• Nakamura, A. et al. Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice. J. Exp. Med. 197, 669–674 (2003).
  CAS PubMed PubMed Central Google Scholar
• Riedemann, N. C. et al. Regulation by C5a of neutrophil activation during sepsis. Immunity 19, 193–202 (2003).
  CAS PubMed Google Scholar
• Abraham, E. et al. Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation. J. Immunol. 170, 5644–5651 (2003).
  CAS PubMed Google Scholar
• Hu, J., Van den Steen, P. E., Dillen, C. & Opdenakker, G. Targeting neutrophil collagenase/matrix metalloproteinase-8 and gelatinase B/matrix metalloproteinase-9 with a peptidomimetic inhibitor protects against endotoxin shock. Biochem. Pharmacol. 70, 535–544 (2005).
  CAS PubMed Google Scholar
• Hu, J. et al. Inhibition of lethal endotoxin shock with an L-pyridylalanine containing metalloproteinase inhibitor selected by high-throughput screening of a new peptide library. Comb. Chem. High Throughput Screen. 9, 599–611 (2006).
  CAS PubMed Google Scholar
• Opdenakker, G., Nelissen, I. & Van Damme, J. Functional roles and therapeutic targeting of gelatinase B and chemokines in multiple sclerosis. Lancet Neurol. 2, 747–756 (2003).
  CAS PubMed Google Scholar
• Gijbels, K. et al. Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein. J. Neurosci. Res. 36, 432–440 (1993).
  CAS PubMed Google Scholar
• Dubois, B. et al. Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions. J. Clin. Invest. 104, 1507–1515 (1999).
  CAS PubMed PubMed Central Google Scholar
• Agrawal, S. et al. Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J. Exp. Med. 203, 1007–1019 (2006). Together with references 64, 165 and 212, gives prototypic examples of knockout studies that demonstrate the role of MMPs in autoimmune diseases.
  CAS PubMed PubMed Central Google Scholar
• Paemen, L., Olsson, T., Söderström, M., Van Damme, J. & Opdenakker, G. Evaluation of gelatinases and IL-6 in the cerebrospinal fluid of patients with optic neuritis, multiple sclerosis and other inflammatory neurological diseases. Eur. J. Neurol. 1, 55–63 (1994).
  CAS PubMed Google Scholar
• Nelissen, I. et al. Gelatinase B/matrix metalloproteinase-9 cleaves interferon-β and is a target for immunotherapy. Brain 126, 1371–1381 (2003).
  PubMed Google Scholar
• Gijbels, K., Galardy, R. E., Steinman, L. Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases. J. Clin. Invest. 94, 2177–2182 (1994). Together with reference 101, illustrates the potential of MMPIs in autoimmune and cardiovascular diseases, respectively.
  CAS PubMed PubMed Central Google Scholar
• Hewson, A. K., Smith, T., Leonard, J. P. & Cuzner, M. L. Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790. Inflamm. Res. 44, 345–349 (1995).
  CAS PubMed Google Scholar
• Norga, K. et al. Prevention of acute autoimmune encephalomyelitis and abrogation of relapses in murine models of multiple sclerosis by the protease inhibitor D-penicillamine. Inflamm. Res. 44, 529–534 (1995).
  CAS PubMed Google Scholar
• Dubois, B. et al. Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine and metacycline in secondary progressive multiple sclerosis. Mult. Scler. 4, 74–78 (1998).
  CAS PubMed Google Scholar
• Brundula, V., Rewcastle, N. B., Metz, L. M., Bernard, C. C. & Yong, V. W. Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis. Brain 125, 1297–1308 (2002).
  PubMed Google Scholar
• Popovic, N. et al. Inhibition of autoimmune encephalomyelitis by a tetracycline. Ann. Neurol. 51, 215–223 (2002).
  CAS PubMed Google Scholar
• Weaver, A. et al. An elevated matrix metalloproteinase (MMP) in an animal model of multiple sclerosis is protective by affecting Th1/Th2 polarization. FASEB J. 19, 1668–1670 (2005).
  CAS PubMed Google Scholar
• Larsen, P. H., Wells, J. E., Stallcup, W. B., Opdenakker, G. & Yong, V. W. Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan. J. Neurosci. 23, 11127–11135 (2003).
  CAS PubMed PubMed Central Google Scholar
• Van den Steen, P. E. et al. Cleavage of denatured natural collagen type II by neutrophil gelatinase B reveals enzyme specificity, post-translational modifications in the substrate, and the formation of remnant epitopes in rheumatoid arthritis. FASEB J. 16, 379–389 (2002).
  CAS PubMed Google Scholar
• Van den Steen, P. E. et al. Generation of glycosylated remnant epitopes from human collagen type II by gelatinase B. Biochemistry 43, 10809–10816 (2004).
  CAS PubMed Google Scholar
• Conway, J. G. et al. Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor. J. Exp. Med. 182, 449–457 (1995).
  CAS PubMed Google Scholar
• DiMartino, M. et al. Anti-arthritic activity of hydroxamic acid-based pseudopeptide inhibitors of matrix metalloproteinases and TNF α processing. Inflamm. Res. 46, 211–215 (1997).
  CAS PubMed Google Scholar
• DiMartino, M. J., High, W., Galloway, W. A. & Crimmin, M. J. Preclinical antiarthritic activity of matrix metalloproteinase inhibitors. Ann. N. Y. Acad. Sci. 732, 411–413 (1994).
  CAS PubMed Google Scholar
• Zhang, Y. et al. Identification and characterization of 4-[[4-(2-butynyloxy)phenyl]sulfonyl]-_N_-hydroxy-2,2-dimethyl-(3S)thiomorpho linecarboxamide (TMI-1), a novel dual tumor necrosis factor-α-converting enzyme/matrix metalloprotease inhibitor for the treatment of rheumatoid arthritis. J. Pharmacol. Exp. Ther. 309, 348–355 (2004).
  CAS PubMed Google Scholar
• Conway, J. G. et al. Inhibition of tumor necrosis factor-α (TNF-α) production and arthritis in the rat by GW3333, a dual inhibitor of TNF-α-converting enzyme and matrix metalloproteinases. J. Pharmacol. Exp. Ther. 298, 900–908 (2001).
  CAS PubMed Google Scholar
• Zernicke, R. F. et al. Administration of systemic matrix metalloproteinase inhibitors maintains bone mechanical integrity in adjuvant arthritis. J. Rheumatol. 24, 1324–1331 (1997).
  CAS PubMed Google Scholar
• Hansson, G. K. & Libby, P. The immune response in atherosclerosis: a double-edged sword. Nature Rev. Immunol. 6, 508–519 (2006). A comprehensive review on atherosclerosis as an inflammatory disease.
  CAS Google Scholar
• Janssens, S. & Lijnen, H. R. What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models? Cardiovasc. Res. 69, 585–594 (2006).
  CAS PubMed Google Scholar
• Tayebjee, M. H., Lip, G. Y. & MacFadyen, R. J. Matrix metalloproteinases in coronary artery disease: clinical and therapeutic implications and pathological significance. Curr. Med. Chem. 12, 917–925 (2005).
  CAS PubMed Google Scholar
• Pawlak, R. et al. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc. Natl Acad. Sci. USA 102, 18201–18206 (2005).
  CAS PubMed PubMed Central Google Scholar
• Lebeurrier, N. et al. The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo. Mol. Cell. Neurosci. 30, 552–558 (2005).
  CAS PubMed Google Scholar
• Yang, Y., Estrada, E. Y., Thompson, J. F., Liu, W. & Rosenberg, G. A. Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J. Cereb. Blood Flow Metab. 27, 697–709 (2007).
  CAS PubMed Google Scholar
• Jian, L. K. & Rosenberg, G. A. Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic. Biol. Med. 39, 71–80 (2005).
  Google Scholar
• Zhao, B. Q. et al. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nature Med. 12, 441–445 (2006).
  CAS PubMed Google Scholar
• Galis, Z. S. et al. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ. Res. 91, 852–859 (2002).
  CAS PubMed Google Scholar
• Cho, A. and Reidy, M. A. Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ. Res. 91, 845–851 (2002).
  CAS PubMed Google Scholar
• Lijnen, H. R., Soloway, P. & Collen, D. Tissue inhibitor of matrix metalloproteinases-1 impairs arterial neointima formation after vascular injury in mice. Circ. Res. 85, 1186–1191 (1999).
  CAS PubMed Google Scholar
• Sluijter, J. P., de Kleijn, D. P. & Pasterkamp, G. Vascular remodeling and protease inhibition — bench to bedside. Cardiovasc. Res. 69, 595–603 (2006).
  CAS PubMed Google Scholar
• Sousa, J. E., Serruys, P. W. & Costa, M. A. New frontiers in cardiology: drug-eluting stents: Part II. Circulation 107, 2383–2389 (2003).
  PubMed Google Scholar
• Lijnen, H. R. et al. Accelerated neointima formation after vascular injury in mice with stromelysin-3 (MMP-11) gene inactivation. Arterioscler. Thromb. Vasc. Biol. 19, 2863–2870 (1999).
  CAS PubMed Google Scholar
• Silence, J., Lupu, F., Collen, D. & Lijnen, H. R. Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP- 3) gene inactivation. Arterioscler. Thromb. Vasc. Biol. 21, 1440–1445 (2001).
  CAS PubMed Google Scholar
• Luttun, A. et al. Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth. Circulation 109, 1408–1414 (2004).
  CAS PubMed Google Scholar
• Heymans, S. et al. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nature Med. 5, 1135–1142 (1999).
  CAS PubMed Google Scholar
• Matsumura, S. et al. Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice. J. Clin. Invest. 115, 599–609 (2005).
  CAS PubMed PubMed Central Google Scholar
• Golub, L. M. et al. Minocycline reduces gingival collagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action. J. Periodontal Res. 18, 516–526 (1983). A pioneering study on the anti-inflammatory effects of tetracyclines, further illustrated in references 103–107.
  CAS PubMed Google Scholar
• Sorsa, T., Tjaderhane, L. & Salo, T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis. 10, 311–318 (2004).
  CAS PubMed Google Scholar
• Sorsa, T. et al. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann. Med. 38, 306–321 (2006).
  CAS PubMed Google Scholar
• Emingil, G. et al. The effect of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis. J. Periodontol. 75, 106–115 (2004).
  CAS PubMed Google Scholar
• Llavaneras, A. et al. A combination of a chemically modified doxycycline and a bisphosphonate synergistically inhibits endotoxin-induced periodontal breakdown in rats. J. Periodontol. 72, 1069–1077 (2001).
  CAS PubMed Google Scholar
• Ramamurthy, N. S. et al. Inhibition of alveolar bone loss by matrix metalloproteinase inhibitors in experimental periodontal disease. J. Periodontal. Res. 37, 1–7 (2002).
  CAS PubMed Google Scholar
• Hautamaki, R. D., Kobayashi, D. K., Senior, R. M. & Shapiro, S. D. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277, 2002–2004 (1997).
  CAS PubMed Google Scholar
• Houghton, A. M. et al. Elastin fragments drive disease progression in a murine model of emphysema. J. Clin. Invest. 116, 753–759 (2006).
  CAS PubMed PubMed Central Google Scholar
• Churg, A. et al. Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-α release. Am. J. Respir. Crit. Care Med. 167, 1083–1089 (2003).
  PubMed Google Scholar
• Liu, Z. et al. The serpin α1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo. Cell 102, 647–655 (2000).
  CAS PubMed Google Scholar
• Selman, M. et al. Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in guinea pigs. Chest 123, 1633–1641 (2003).
  CAS PubMed Google Scholar
• Gueders, M. M. et al. Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. J. Immunol. 175, 2589–2597 (2005).
  CAS PubMed Google Scholar
• Corry, D. B. et al. Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency. Nature Immunol. 3, 347–353 (2002).
  CAS Google Scholar
• Van Lint, P. et al. Resistance of collagenase-2 (matrix metalloproteinase-8)-deficient mice to TNF-induced lethal hepatitis. J. Immunol. 175, 7642–7649 (2005).
  CAS PubMed Google Scholar
• Cataldo, D. D. et al. Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation. Am. J. Pathol. 161, 491–498 (2002).
  CAS PubMed PubMed Central Google Scholar
• Vermaelen, K. Y. et al. Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma. J. Immunol. 171, 1016–1022 (2003).
  CAS PubMed Google Scholar
• Corry, D. B. et al. Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J. 18, 995–997 (2004).
  CAS PubMed Google Scholar
• Kumagai, K. et al. The involvement of matrix metalloproteinases in basement membrane injury in a murine model of acute allergic airway inflammation. Clin. Exp. Allergy. 32, 1527–1534 (2002).
  CAS PubMed Google Scholar
• Kumagai, K. et al. Inhibition of matrix metalloproteinases prevents allergen-induced airway inflammation in a murine model of asthma. J. Immunol. 162, 4212–4219 (1999).
  CAS PubMed Google Scholar
• Lee, K. S., Jin, S. M., Kim, S. S. & Lee, Y. C. Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate-induced asthma. J. Allergy Clin. Immunol. 113, 902–909 (2004).
  CAS PubMed Google Scholar
• Lee, Y. C. et al. A murine model of toluene diisocyanate-induced asthma can be treated with matrix metalloproteinase inhibitor. J. Allergy Clin. Immunol. 108, 1021–1026 (2001).
  CAS PubMed Google Scholar
• Corbel, M. et al. Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat. J. Pathol. 193, 538–545 (2001).
  CAS PubMed Google Scholar
• Tan, R. J. et al. Matrix metalloproteinases promote inflammation and fibrosis in asbestos-induced lung injury in mice. Am. J. Respir. Cell Mol. Biol. 35, 289–297 (2006).
  CAS PubMed PubMed Central Google Scholar
• Zuo, F. et al. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc. Natl Acad. Sci. USA 99, 6292–6297 (2002).
  CAS PubMed PubMed Central Google Scholar
• Manoury, B. et al. Macrophage metalloelastase (MMP-12) deficiency does not alter bleomycin-induced pulmonary fibrosis in mice. J. Inflamm. (Lond) 3, 2 (2006).
  Google Scholar
• Li, Q., Park, P. W., Wilson, C. L. & Parks, W. C. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell. 111, 635–646 (2002).
  CAS PubMed Google Scholar
• Greenlee, K. J. et al. Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation. J. Immunol. 177, 7312–7321 (2006).
  CAS PubMed Google Scholar
• Wielockx, B. et al. Inhibition of matrix metalloproteinases blocks lethal hepatitis and apoptosis induced by tumor necrosis factor and allows safe antitumor therapy. Nature Med. 7, 1202–1208 (2001).
  CAS PubMed Google Scholar
• Sitia, G. et al. MMPs are required for recruitment of antigen-nonspecific mononuclear cells into the liver by CTLs. J. Clin. Invest. 113, 1158–1167 (2004).
  CAS PubMed PubMed Central Google Scholar
• Muller-Pillasch, F. et al. The influence of transforming growth factor β1 on the expression of genes coding for matrix metalloproteinases and tissue inhibitors of metalloproteinases during regeneration from cerulein-induced pancreatitis. Pancreas 15, 168–175 (1997).
  CAS PubMed Google Scholar
• Descamps, F. J., Martens, E., Ballaux, F., Geboes, K. & Opdenakker, G. In vivo activation of gelatinase B/MMP-9 by trypsin in acute pancreatitis is a permissive factor in streptozotocin-induced diabetes. J. Pathol. 204, 555–561 (2004).
  CAS PubMed Google Scholar
• Descamps, F. J. et al. Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin. FASEB J. 17, 887–889 (2003).
  CAS PubMed Google Scholar
• Leppert, D. et al. Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood–brain barrier damage and neurological sequelae. Clin. Infect. Dis. 31, 80–84 (2000).
  CAS PubMed Google Scholar
• Leib, S. L. et al. Inhibition of matrix metalloproteinases and tumour necrosis factor α converting enzyme as adjuvant therapy in pneumococcal meningitis. Brain 124, 1734–1742 (2001).
  CAS PubMed Google Scholar
• Bottcher, T., Spreer, A., Azeh, I., Nau, R. & Gerber, J. Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis. Neurosci. Lett. 338, 201–204 (2003).
  CAS PubMed Google Scholar
• Yong, V. W. Metalloproteinases: mediators of pathology and regeneration in the CNS. Nature Rev. Neurosci. 6, 931–944 (2005). Together with reference 19, gives a critical review of the protective and detrimental roles played by metalloproteinases, as deduced from knockout studies.
  CAS Google Scholar
• Porter, S., Clark, I. M., Kevorkian, L. & Edwards, D. R. The ADAMTS metalloproteinases. Biochem. J. 386, 15–27 (2005).
  CAS PubMed PubMed Central Google Scholar
• Opdenakker, G., Van den Steen, P. E., Laureys, G., Hunninck, K. & Arnold, B. Neutralizing antibodies in gene-defective hosts. Trends Immunol. 24, 94–100 (2003).
  CAS PubMed Google Scholar
• Grams, F. et al. X-ray structures of human neutrophil collagenase complexed with peptide hydroxamate and peptide thiol inhibitors. Implications for substrate binding and rational drug design. Eur. J. Biochem. 228, 830–841 (1995). Together with references 32–34 and 142, gives exemplary primary and review literature on the crystallography of MMPs and MMPIs.
  CAS PubMed Google Scholar
• Castelhano, A. L. et al. Novel indolactam-based inhibitors of matrix metalloproteinases. Bioorg. Med. Chem. Lett. 5, 1415–1420 (2006).
  Google Scholar
• Lovejoy, B. et al. Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor. Science 263, 375–377 (1994).
  CAS PubMed Google Scholar
• Brown, P. D. Matrix metalloproteinase inhibitors in the treatment of cancer. Med. Oncol. 14, 1–10 (1997).
  CAS PubMed Google Scholar
• Wojtowicz-Praga, S. et al. Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J. Clin. Oncol. 16, 2150–2156 (1998).
  CAS PubMed Google Scholar
• Campbell, D. A. et al. Malonyl α-mercaptoketones and α-mercaptoalcohols, a new class of matrix metalloproteinase inhibitors. Bioorg. Med. Chem. Lett. 8, 1157–1162 (1998).
  CAS PubMed Google Scholar
• Fernandez, F. G. et al. Inhibition of obliterative airway disease development in murine tracheal allografts by matrix metalloproteinase-9 deficiency. Am. J. Transplant. 5, 671–683 (2005).
  CAS PubMed Google Scholar
• Warner, R. L. et al. Role of stromelysin 1 and gelatinase B in experimental acute lung injury. Am. J. Respir. Cell Mol. Biol. 24, 537–544 (2001).
  CAS PubMed Google Scholar
• McGuire, J. K., Li, Q., Parks, W. C. Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am. J. Pathol. 162, 1831–1843 (2003).
  CAS PubMed PubMed Central Google Scholar
• Dunsmore, S. E. et al. Matrilysin expression and function in airway epithelium. J. Clin. Invest. 102, 1321–1331 (1998).
  CAS PubMed PubMed Central Google Scholar
• Lanone, S. et al. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and-12 in IL-13-induced inflammation and remodeling. J. Clin. Invest. 110, 463–474 (2002).
  CAS PubMed PubMed Central Google Scholar
• Betsuyaku, T., Fukuda, Y., Parks, W. C., Shipley, J. M. & Senior, R. M. Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin. Am. J. Pathol. 157, 525–535 (2000).
  CAS PubMed PubMed Central Google Scholar
• McMillan, S. J. et al. Matrix metalloproteinase-9 deficiency results in enhanced allergen-induced airway inflammation. J. Immunol. 172, 2586–2594 (2004).
  CAS PubMed Google Scholar
• Warner, R. L. et al. The role of metalloelastase in immune complex-induced acute lung injury. Am. J. Pathol. 158, 2139–2144 (2001).
  CAS PubMed PubMed Central Google Scholar
• Irie, K. et al. Impaired alveolization in mice deficient in membrane-type matrix metalloproteinase 1 (MT1–MMP). Med. Mol. Morphol. 38, 43–46 (2005).
  CAS PubMed Google Scholar
• Atkinson, J. J. et al. Membrane-type 1 matrix metalloproteinase is required for normal alveolar development. Dev. Dyn. 232, 1079–1090 (2005).
  CAS PubMed Google Scholar
• Garg, P. et al. Selective ablation of matrix metalloproteinase-2 exacerbates experimental colitis: contrasting role of gelatinases in the pathogenesis of colitis. J. Immunol. 177, 4103–4112 (2006).
  CAS PubMed Google Scholar
• Wilson, C. L. et al. Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286, 113–117 (1999). Together with references 13, 127, 148, 172, 209 and 211, gives an excellent illustration of how Mmp -knockout mice can be used to define novel substrates. Such substrate conversion might be used in the future as a readout for testing the specificity of MMPIs in vivo.
  CAS PubMed Google Scholar
• Kolaczkowska, E. et al. Enhanced early vascular permeability in gelatinase B (MMP-9)-deficient mice: putative contribution of COX-1-derived PGE2 of macrophage origin. J. Leukoc. Biol. 80, 125–132 (2006).
  CAS PubMed Google Scholar
• Kolaczkowska, E. et al. Gelatinase B/matrix metalloproteinase-9 contributes to cellular infiltration in a murine model of zymosan peritonitis. Immunobiology 211, 137–148 (2006).
  CAS PubMed Google Scholar
• Renckens, R. et al. Matrix metalloproteinase-9 deficiency impairs host defense against abdominal sepsis. J. Immunol. 176, 3735–3741 (2006).
  CAS PubMed Google Scholar
• Castaneda, F. E. et al. Targeted deletion of metalloproteinase 9 attenuates experimental colitis in mice: central role of epithelial-derived MMP. Gastroenterology 129, 1991–2008 (2005).
  CAS PubMed Google Scholar
• Uchinami, H., Seki, E., Brenner, D. A. & D'Armiento, J. Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis. Hepatology 44, 420–429 (2006).
  CAS PubMed Google Scholar
• Caterina, J. J. et al. Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype. J. Biol. Chem. 277, 49598–49604 (2002).
  CAS PubMed Google Scholar
• Beniash, E., Skobe, Z. & Bartlett, J. D. Formation of the dentino-enamel interface in enamelysin (MMP-20)-deficient mouse incisors. Eur. J. Oral Sci. 114 (Suppl 1), 24–29 (2006).
  CAS PubMed Google Scholar
• Itoh, T. et al. The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis. J. Immunol. 169, 2643–2647 (2002).
  CAS PubMed Google Scholar
• Mudgett, J. S. et al. Susceptibility of stromelysin1-deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum. 41, 110–121 (1998).
  CAS PubMed Google Scholar
• Calander, A. M. et al. Matrix metalloproteinase-9 (gelatinase B) deficiency leads to increased severity of _Staphylococcus aureus_-triggered septic arthritis. Microbes Infect. 8, 1434–1439 (2006).
  CAS PubMed Google Scholar
• Vu, T. H. et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93, 411–422 (1998). Together with the reports on Mmp3 and Mmp7 knockouts, a pioneering study showing the spontaneous phenotypic characteristics of Mmp knockouts.
  CAS PubMed PubMed Central Google Scholar
• Ortega, N., Behonick, D. J., Colnot, C., Cooper, D. N. & Werb, Z. Galectin-3 is a downstream regulator of matrix metalloproteinase-9 function during endochondral bone formation. Mol. Biol. Cell 16, 3028–3039 (2005).
  CAS PubMed PubMed Central Google Scholar
• Wright, R. W. et al. Medial collateral ligament healing in macrophage metalloelastase (MMP-12)-deficient mice. J. Orthop. Res. 24, 2106–2113 (2006).
  CAS PubMed Google Scholar
• Stickens, D. et al. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development 131, 5883–5895 (2004).
  CAS PubMed Google Scholar
• Holmbeck, K. et al. The metalloproteinase MT1–MMP is required for normal development and maintenance of osteocyte processes in bone. J. Cell Sci. 118, 147–156 (2005).
  CAS PubMed Google Scholar
• Hsu, J. Y. et al. Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. J. Neurosci. 26, 9841–9850 (2006).
  CAS PubMed PubMed Central Google Scholar
• Tang, J. et al. MMP-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. J. Cereb. Blood Flow Metab. 24, 1133–1145 (2004).
  PubMed Google Scholar
• Larsen, P. H., DaSilva, A. G., Conant, K. & Yong, V. W. Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and-12 null mice. J. Neurosci. 26, 2207–2214 (2006).
  CAS PubMed PubMed Central Google Scholar
• Asahi, M. et al. Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J. Cereb. Blood Flow Metab. 20, 1681–1689 (2000).
  CAS PubMed Google Scholar
• Dewil, M. et al. Role of matrix metalloproteinase-9 in a mouse model for amyotrophic lateral sclerosis. Neuroreport 16, 321–324 (2005).
  CAS PubMed Google Scholar
• Wells, J. E. et al. An adverse role for matrix metalloproteinase 12 after spinal cord injury in mice. J. Neurosci. 23, 10107–10115 (2003).
  CAS PubMed PubMed Central Google Scholar
• Larsen, P. H. & Yong, V. W. The expression of matrix metalloproteinase-12 by oligodendrocytes regulates their maturation and morphological differentiation. J. Neurosci. 24, 7597–7603 (2004).
  CAS PubMed PubMed Central Google Scholar
• Komori, K. et al. Absence of mechanical allodynia and Aβ-fiber sprouting after sciatic nerve injury in mice lacking membrane-type 5 matrix metalloproteinase. FEBS Lett. 557, 125–128 (2004).
  CAS PubMed Google Scholar
• Campbell, L. G. et al. Different roles for matrix metalloproteinase-2 and matrix metalloproteinase-9 in the pathogenesis of cardiac allograft rejection. Am. J. Transplant. 5, 517–528 (2005).
  CAS PubMed Google Scholar
• Samolov, B. et al. Delayed inflammation-associated corneal neovascularization in MMP-2-deficient mice. Exp. Eye Res. 80, 159–166 (2005).
  CAS PubMed Google Scholar
• Ohno-Matsui, K. et al. Reduced retinal angiogenesis in MMP-2-deficient mice. Invest. Ophthalmol. Vis. Sci. 44, 5370–5375 (2003).
  PubMed Google Scholar
• Berglin, L. et al. Reduced choroidal neovascular membrane formation in matrix metalloproteinase-2-deficient mice. Invest. Ophthalmol. Vis. Sci. 44, 403–408 (2003).
  PubMed Google Scholar
• Basalyga, D. M. et al. Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases. Circulation 110, 3480–3487 (2004).
  CAS PubMed PubMed Central Google Scholar
• Lambert, V. et al. MMP-2 and MMP-9 synergize in promoting choroidal neovascularization. FASEB J. 17, 2290–2292 (2003).
  CAS PubMed Google Scholar
• Longo, G. M. et al. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J. Clin. Invest. 110, 625–632 (2002).
  CAS PubMed PubMed Central Google Scholar
• Ikonomidis, J. S. et al. Effects of deletion of the matrix metalloproteinase 9 gene on development of murine thoracic aortic aneurysms. Circulation 112, I242–I248 (2005).
  PubMed Google Scholar
• Sarman, S., van der Ploeg, I., Seregard, S. & Kvanta, A. Retinal vascular development and pathologic retinal angiogenesis are not impaired in matrix metalloproteinase-2 deficient mice. Curr. Eye Res. 30, 259–267 (2005).
  CAS PubMed Google Scholar
• Kuzuya, M. et al. Effect of MMP-2 deficiency on atherosclerotic lesion formation in Apoe-deficient mice. Arterioscler. Thromb. Vasc. Biol. 26, 1120–1125 (2006).
  CAS PubMed Google Scholar
• Mukherjee, R. et al. Time-dependent changes in myocardial structure following discrete injury in mice deficient of matrix metalloproteinase-3. J. Mol. Cell. Cardiol. 39, 259–268 (2005).
  CAS PubMed Google Scholar
• Kure, T. et al. Corneal neovascularization after excimer keratectomy wounds in matrilysin-deficient mice. Invest. Ophthalmol. Vis. Sci. 44, 137–144 (2003).
  PubMed Google Scholar
• Pyo, R. et al. Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J. Clin. Invest. 105, 1641–1649 (2000).
  CAS PubMed PubMed Central Google Scholar
• Heissig, B. et al. Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. J. Exp. Med. 202, 739–750 (2005).
  CAS PubMed PubMed Central Google Scholar
• Ovechkin, A. V. et al. Role of matrix metalloproteinase-9 in endothelial apoptosis in chronic heart failure in mice. J. Appl. Physiol. 99, 2398–2405 (2005).
  CAS PubMed Google Scholar
• Heymans, S. et al. Loss or inhibition of uPA or MMP-9 attenuates LV remodeling and dysfunction after acute pressure overload in mice. Am. J. Pathol. 166, 15–25 (2005).
  CAS PubMed PubMed Central Google Scholar
• Lindsey, M. L. et al. Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 290, H232–H239 (2006).
  CAS PubMed Google Scholar
• Johnson, C., Sung, H. J., Lessner, S. M., Fini, M. E. & Galis, Z. S. Matrix metalloproteinase-9 is required for adequate angiogenic revascularization of ischemic tissues: potential role in capillary branching. Circ. Res. 94, 262–268 (2004).
  CAS PubMed Google Scholar
• Jost, M. et al. Earlier onset of tumoral angiogenesis in matrix metalloproteinase-19-deficient mice. Cancer Res. 66, 5234–5241 (2006).
  CAS PubMed Google Scholar
• Sung, H. J. et al. Matrix metalloproteinase 9 facilitates collagen remodeling and angiogenesis for vascular constructs. Tissue Eng. 11, 267–276 (2005).
  CAS PubMed Google Scholar
• Choi, E. T. et al. Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 25, 1020–1025 (2005).
  CAS PubMed Google Scholar
• Longo, G. M. et al. MMP-12 has a role in abdominal aortic aneurysms in mice. Surgery 137, 457–462 (2005).
  PubMed Google Scholar
• Wang, M. et al. Matrix metalloproteinase deficiencies affect contact hypersensitivity: stromelysin-1 deficiency prevents the response and gelatinase B deficiency prolongs the response. Proc. Natl Acad. Sci. USA 96, 6885–6889 (1999).
  CAS PubMed PubMed Central Google Scholar
• Li, C. K. et al. Impaired immunity to intestinal bacterial infection in stromelysin-1 (matrix metalloproteinase-3)-deficient mice. J. Immunol. 173, 5171–5179 (2004).
  CAS PubMed Google Scholar
• Powell, W. C., Fingleton, B., Wilson, C. L., Boothby, M. & Matrisian, L. M. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Curr. Biol. 9, 1441–1447 (1999).
  CAS PubMed Google Scholar
• Haro, H. et al. Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption. J. Clin. Invest. 105, 133–141 (2000).
  CAS PubMed PubMed Central Google Scholar
• Haro, H. et al. Matrix metalloproteinase-7-dependent release of tumor necrosis factor-α in a model. J. Clin. Invest. 150, 143–150 (2000).
  Google Scholar
• Balbin, M. et al. Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nature Genet. 35, 252–257 (2003).
  CAS PubMed Google Scholar
• Senft, A. P., Korfhagen, T. R., Whitsett, J. A., Shapiro, S. D. & LeVine, A. M. Surfactant protein-D regulates soluble CD14 through matrix metalloproteinase-12. J. Immunol. 174, 4953–4959 (2005).
  CAS PubMed Google Scholar
• Pflugfelder, S. C. et al. Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye. Am. J. Pathol. 166, 61–71 (2005).
  CAS PubMed PubMed Central Google Scholar
• Robinson, S. N., Seina, S. M., Gohr, J. C. & Sharp, J. G. Hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor and erythropoietin in the absence of matrix metalloproteinase-9. Stem Cells Dev. 14, 317–328 (2005).
  CAS PubMed Google Scholar
• Liu, Z. et al. Gelatinase B-deficient mice are resistant to experimental bullous pemphigoid. J. Exp. Med. 188, 475–482 (1998).
  CAS PubMed PubMed Central Google Scholar
• Ratzinger, G. et al. Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin. J. Immunol. 168, 4361–4371 (2002).
  CAS PubMed Google Scholar
• Shipley, J. M., Wesselschmidt, R. L., Kobayashi, D. K., Ley, T. J. & Shapiro, S. D. Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc. Natl Acad. Sci. USA 93, 3942–3946 (1996).
  CAS PubMed PubMed Central Google Scholar
• Koistinaho, M. et al. Minocycline protects against permanent cerebral ischemia in wild type but not in matrix metalloprotease-9-deficient mice. J. Cereb. Blood Flow Metab. 25, 460–467 (2005).
  CAS PubMed Google Scholar
• Jodele, S. et al. The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. Cancer Res. 65, 3200–3208 (2005).
  CAS PubMed Google Scholar
• Topp, S. A., Upadhya, G. A. & Strasberg, S. M. Cold preservation of isolated sinusoidal endothelial cells in MMP 9 knockout mice: effect on morphology and platelet adhesion. Liver Transpl. 10, 1041–1048 (2004).
  PubMed Google Scholar
• Andarawewa, K. L. et al. Stromelysin-3 is a potent negative regulator of adipogenesis participating to cancer cell-adipocyte interaction/crosstalk at the tumor invasive front. Cancer Res. 65, 10862–10871 (2005).
  CAS PubMed Google Scholar
• Pendas, A. M. et al. Diet-induced obesity and reduced skin cancer susceptibility in matrix metalloproteinase 19-deficient mice. Mol. Cell. Biol. 24, 5304–5313 (2004).
  CAS PubMed PubMed Central Google Scholar
• Kang, H. R., Cho, S. J., Lee, C. G., Homer, R. J. & Elias, J. A. Transforming growth factor (TGF)-β stimulates pulmonary fibrosis and inflammation via a Bax-dependent, bid-activated pathway that involves matrix metalloproteinase-12. J. Biol. Chem. 282, 7723–7732 (2007).
  CAS PubMed Google Scholar