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Mouse Models of MMP and TIMP Function

  • Sean E. Gill
  • Sean Y. Kassim
  • Timothy P. Birkland
  • William C. Parks
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 622)

Abstract

As their name implies, matrix metalloproteinases (MMPs) are thought to be responsible for the turnover of connective tissue proteins, a function that is indeed performed by some family members. However, matrix degradation is possibly not the predominant function of these enzymes. Several studies have demonstrated that MMPs also act on a variety of non-matrix extracellular proteins, such as cytokines, chemokines, receptors, junctional proteins, and antimicrobial peptides, to mediate a wide range of biological processes, such as repair, immunity, and angiogenesis. Our understanding of the many, diverse and, at times, unexpected functions of MMPs largely arose from the use of gene-targeted mice. In this chapter, we discuss the phenotypes of some MMP-deficient and TIMP-null mice and strategies and pitfalls in targeted mutagenesis.

Key words

Knockout knockdown substrate identification conditional inhibitors tissue specific compensation redundancy 

References

  1. 1.
    Lopez-Otin, C. and Overall, C. M. (2002) Protease degradomics: a new challenge for proteomics. Nat Rev Mol Cell Biol 3, 509–519.PubMedCrossRefGoogle Scholar
  2. 2.
    Mott, J. D. and Werb, Z. (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16, 558–564.PubMedCrossRefGoogle Scholar
  3. 3.
    Parks, W. C., Wilson, C. L., and Lopez-Boado, Y. S. (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4, 617–629.PubMedCrossRefGoogle Scholar
  4. 4.
    Agrawal, S. M., Lau, L., and Yong, V. W. (2008) MMPs in the central nervous system: where the good guys go bad. Semin Cell Dev Biol 19, 42–51.PubMedCrossRefGoogle Scholar
  5. 5.
    Manicone, A. M. and McGuire, J. K. (2008) Matrix metalloproteinases as modulators of inflammation. Semin Cell Dev Biol 19, 34–41.PubMedCrossRefGoogle Scholar
  6. 6.
    Page-McCaw, A., Ewald, A. J., and Werb, Z. (2007) Matrix metalloproteinases and the regulation of tissue remodeling. Nat Rev Mol Cell Biol 8, 221-233.PubMedCrossRefGoogle Scholar
  7. 7.
    Egeblad, M. and Werb, Z. (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2, 161–174.PubMedCrossRefGoogle Scholar
  8. 8.
    Van Lint, P. and Libert, C. (2007) Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol 82, 1375–1381.PubMedCrossRefGoogle Scholar
  9. 9.
    Ra, H. J. and Parks, W. C. (2007) Control of matrix metalloproteinase catalytic activity. Matrix Biol 26, 587–596.PubMedCrossRefGoogle Scholar
  10. 10.
    Massova, I., Kotra, L. P., Fridman, R., and Mobashery, S. (1998) Matrix metalloproteinases: structures, evolution, and diversification. FASEB J 12, 1075–1095.PubMedGoogle Scholar
  11. 11.
    Nagase, H., Visse, R., and Murphy, G. (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69, 562–573.PubMedCrossRefGoogle Scholar
  12. 12.
    Maskos, K. and Bode, W. (2003) Structural basis of matrix metalloproteinases and tissue inhibitors of metalloproteinases. Mol Biotechnol 25, 241–266.PubMedCrossRefGoogle Scholar
  13. 13.
    Gill, S. E. and Parks, W. C. (2008) Metalloproteinases and their inhibitors: Regulators of wound healing. Int J Biochem Cell Biol 40, 1334–1347.PubMedCrossRefGoogle Scholar
  14. 14.
    Campbell, E. J., Campbell, M. A., Boukedes, S. S., and Owen, C. A. (1999) Quantum proteolysis by neutrophils: implications for pulmonary emphysema in alpha 1-antitrypsin deficiency. J Clin Invest 104, 337–344.PubMedCrossRefGoogle Scholar
  15. 15.
    Baker, A. H., Edwards, D. R., and Murphy, G. (2002) Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci 115, 3719–3727.PubMedCrossRefGoogle Scholar
  16. 16.
    Leco, K. J., Apte, S. S., Taniguchi, G. T., Hawkes, S. P., Khokha, R., Schultz, G. A., and Edwards, D. R. (1997) Murine tissue inhibitor of metalloproteinases-4 (Timp-4): cDNA isolation and expression in adult mouse tissues. FEBS Lett 401, 213–217.PubMedCrossRefGoogle Scholar
  17. 17.
    Oh, J., Takahashi, R., Kondo, S., Mizoguchi, A., Adachi, E., Sasahara, R. M., Nishimura, S., Imamura, Y., Kitayama, H., Alexander, D. B., Ide, C., Horan, T. P., Arakawa, T., Yoshida, H., Nishikawa, S., Itoh, Y., Seiki, M., Itohara, S., Takahashi, C., and Noda, M. (2001) The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107, 789–800.PubMedCrossRefGoogle Scholar
  18. 18.
    Kassim, S. Y., Fu, X., Liles, W. C., Shapiro, S. D., Parks, W. C., and Heinecke, J. W. (2005) NADPH oxidase restrains the matrix metalloproteinase activity of macrophages. J Biol Chem 280, 30201–30205.PubMedCrossRefGoogle Scholar
  19. 19.
    Brew, K., Dinakarpandian, D., and Nagase, H. (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477, 267–283.PubMedCrossRefGoogle Scholar
  20. 20.
    Yu, W. H., Yu, S., Meng, Q., Brew, K., and Woessner, J. F., Jr. (2000) TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J Biol Chem 275, 31226–31232.PubMedCrossRefGoogle Scholar
  21. 21.
    Caterina, J. J., Yamada, S., Caterina, N. C., Longenecker, G., Holmback, K., Shi, J., Yermovsky, A. E., Engler, J. A., and Birkedal-Hansen, H. (2000) Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2(Timp-2) gene alters proMMP-2 activation. J Biol Chem 275, 26416–26422.PubMedCrossRefGoogle Scholar
  22. 22.
    Wang, Z., Juttermann, R., and Soloway, P. D. (2000) TIMP-2 is required for efficient activation of proMMP-2 in vivo. J Biol Chem 275, 26411–26415.PubMedCrossRefGoogle Scholar
  23. 23.
    Seo, D. W., Li, H., Guedez, L., Wingfield, P. T., Diaz, T., Salloum, R., Wei, B. Y., and Stetler-Stevenson, W. G. (2003) TIMP-2 mediated inhibition of angiogenesis: an MMP-independent mechanism. Cell 114, 171–180.PubMedCrossRefGoogle Scholar
  24. 24.
    Qi, J. H., Ebrahem, Q., Moore, N., Murphy, G., Claesson-Welsh, L., Bond, M., Baker, A., and Anand-Apte, B. (2003) A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med 9, 407–415.PubMedCrossRefGoogle Scholar
  25. 25.
    McQuibban, G. A., Gong, J. H., Tam, E. M., McCulloch, C. A., Clark-Lewis, I., and Overall, C. M. (2000) Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289, 1202–1206.PubMedCrossRefGoogle Scholar
  26. 26.
    auf dem Keller, U., Doucet, A., and Overall, C. M. (2007) Protease research in the era of systems biology. Biol Chem 388, 1159–1162.PubMedGoogle Scholar
  27. 27.
    Holmbeck, K., Bianco, P., Caterina, J., Yamada, S., Kromer, M., Kuznetsov, S. A., Mankani, M., Robey, P. G., Poole, A. R., Pidoux, I., Ward, J. M., and Birkedal-Hansen, H. (1999) MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99, 81–92.PubMedCrossRefGoogle Scholar
  28. 28.
    Powell, W. C., Fingleton, B., Wilson, C. L., Boothby, M., and Matrisian, L. M. (1999) The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Curr Biol 9, 1441–1447.PubMedCrossRefGoogle Scholar
  29. 29.
    McCawley, L. J. and Matrisian, L. M. (2001) Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol 13, 534–540.PubMedCrossRefGoogle Scholar
  30. 30.
    Folgueras, A. R., Pendas, A. M., Sanchez, L. M., and Lopez-Otin, C. (2004) Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol 48, 411–424.PubMedCrossRefGoogle Scholar
  31. 31.
    Janssens, S. and Lijnen, H. R. (2006) What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models? Cardiovasc Res 69, 585–594.PubMedCrossRefGoogle Scholar
  32. 32.
    Hu, J., Van den Steen, P. E., Sang, Q. X., and Opdenakker, G. (2007) Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 6, 480–498.PubMedCrossRefGoogle Scholar
  33. 33.
    Greenlee, K. J., Werb, Z., and Kheradmand, F. (2007) Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted. Physiol Rev 87, 69–98.PubMedCrossRefGoogle Scholar
  34. 34.
    Zeisberg, M., Khurana, M., Rao, V. H., Cosgrove, D., Rougier, J. P., Werner, M. C., Shield, C. F., 3rd, Werb, Z., and Kalluri, R. (2006) Stage-specific action of matrix metalloproteinases influences progressive hereditary kidney disease. PLoS Med 3, e100.PubMedCrossRefGoogle Scholar
  35. 35.
    Rudolph-Owen, L. A., Hulboy, D. L., Wilson, C. L., Mudgett, J., and Matrisian, L. M. (1997) Coordinate expression of matrix metalloproteinase family members in the uterus of normal, matrilysin-deficient, and stromelysin-1-deficient mice. Endocrinology 138, 4902–4911.PubMedCrossRefGoogle Scholar
  36. 36.
    Sahin, U., Weskamp, G., Kelly, K., Zhou, H. M., Higashiyama, S., Peschon, J., Hartmann, D., Saftig, P., and Blobel, C. P. (2004) Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol 164, 769–779.PubMedCrossRefGoogle Scholar
  37. 37.
    Coussens, L. M., Fingleton, B., and Matrisian, L. M. (2002) Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295, 2387–2392.PubMedCrossRefGoogle Scholar
  38. 38.
    Wilson, C. L., Heppner, K. J., Labosky, P. A., Hogan, B. L. M., and Matrisian, L. M. (1997) Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A 94, 1402–1407.PubMedCrossRefGoogle Scholar
  39. 39.
    Dunsmore, S. E., Saarialho-Kere, U. K., Roby, J. D., Wilson, C. L., Matrisian, L. M., Welgus, H. G., and Parks, W. C. (1998) Matrilysin expression and function in airway epithelium. J Clin Invest 102, 1321–1331.PubMedCrossRefGoogle Scholar
  40. 40.
    McGuire, J. K., Li, Q., and Parks, W. C. (2003) Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am J Pathol 162, 1831–1843.PubMedCrossRefGoogle Scholar
  41. 41.
    Li, Q., Park, P. W., Wilson, C. L., and Parks, W. C. (2002) Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 111, 635–646.PubMedCrossRefGoogle Scholar
  42. 42.
    Swee, M., Wilson, C. L., Wang, Y., McGuire, J. K., and Parks, W. C. (2008) Matrilysin (MMP7) controls neutrophil egress and activation through generation of chemokine gradients. J Leuko Biol 83, 1402–1412.Google Scholar
  43. 43.
    Coussens, L. M., Tinkle, C. L., Hanahan, D., and Werb, Z. (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103, 481–490.PubMedCrossRefGoogle Scholar
  44. 44.
    Hotary, K., Allen, E., Punturieri, A., Yana, I., and Weiss, S. J. (2000) Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J Cell Biol 149, 1309–1323.PubMedCrossRefGoogle Scholar
  45. 45.
    Hotary, K. B., Allen, E. D., Brooks, P. C., Datta, N. S., Long, M. W., and Weiss, S. J. (2003) Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell 114, 33–45.PubMedCrossRefGoogle Scholar
  46. 46.
    McCawley, L. J., Crawford, H. C., King, L. E., Jr., Mudgett, J., and Matrisian, L. M. (2004) A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Res 64, 6965–6972.PubMedCrossRefGoogle Scholar
  47. 47.
    Balbin, M., Fueyo, A., Tester, A. M., Pendas, A. M., Pitiot, A. S., Astudillo, A., Overall, C. M., Shapiro, S. D., and Lopez-Otin, C. (2003) Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet 35, 252–257.PubMedCrossRefGoogle Scholar
  48. 48.
    Yana, I., Sagara, H., Takaki, S., Takatsu, K., Nakamura, K., Nakao, K., Katsuki, M., Taniguchi, S., Aoki, T., Sato, H., Weiss, S. J., and Seiki, M. (2007) Crosstalk between neovessels and mural cells directs the site-specific expression of MT1-MMP to endothelial tip cells. J Cell Sci 120, 1607–1614.PubMedCrossRefGoogle Scholar
  49. 49.
    Zhou, H. E., Zhang, X., and Nothnick, W. B. (2004) Disruption of the TIMP-1 gene product is associated with accelerated endometrial gland formation during early postnatal uterine development. Biol Reprod 71, 534–539.PubMedCrossRefGoogle Scholar
  50. 50.
    Olson, E. N., Arnold, H.-H., Rigby, P. W. J., and Wold, B. J. (1996) Know your neighbors. Three phenotypes in null mutants of the myogenic bHLH gene MRF4. Cell 85, 1–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Hayashi, S., Lewis, P., Pevny, L., and McMahon, A. P. (2002) Efficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strain. Mech Dev 119(Suppl 1), S97–S101.PubMedCrossRefGoogle Scholar
  52. 52.
    Soriano, P. (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21, 70–71.PubMedCrossRefGoogle Scholar
  53. 53.
    Collins, F. S., Rossant, J., and Wurst, W. (2007) A mouse for all reasons. Cell 128, 9–13.PubMedCrossRefGoogle Scholar
  54. 54.
    Cheng, J., Sauthoff, H., Huang, Y., Kutler, D. I., Bajwa, S., Rom, W. N., and Hay, J. G. (2007) Human matrix metalloproteinase-8 gene delivery increases the oncolytic activity of a replicating adenovirus. Mol Ther 15, 1982–1990.PubMedCrossRefGoogle Scholar
  55. 55.
    Wilson, C. L., Ouellette, A. J., Satchell, D. P., Ayabe, T., Lopez-Boado, Y. S., Stratman, J. L., Hultgren, S. J., Matrisian, L. M., and Parks, W. C. (1999) Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286, 113–117.PubMedCrossRefGoogle Scholar
  56. 56.
    Lynch, C. C., Hikosaka, A., Acuff, H. B., Martin, M. D., Kawai, N., Singh, R. K., Vargo-Gogola, T. C., Begtrup, J. L., Peterson, T. E., Fingleton, B., Shirai, T., Matrisian, L. M., and Futakuchi, M. (2005) MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 7, 485–496.PubMedCrossRefGoogle Scholar
  57. 57.
    Haro, H., Crawford, H. C., Fingleton, B., Shinomiya, K., Spengler, D. M., and Matrisian, L. M. (2000) Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption. J Clin Invest 105, 143–150.PubMedCrossRefGoogle Scholar
  58. 58.
    Filippov, S., Caras, I., Murray, R., Matrisian, L. M., Chapman, H. A., Jr., Shapiro, S., and Weiss, S. J. (2003) Matrilysin-dependent elastolysis by human macrophages. J Exp Med 198, 925–935.PubMedCrossRefGoogle Scholar
  59. 59.
    Sawey, E. T., Johnson, J. A., and Crawford, H. C. (2007) Matrix metalloproteinase 7 controls pancreatic acinar cell transdifferentiation by activating the Notch signaling pathway. Proc Natl Acad Sci U S A 104, 19327–19332.PubMedCrossRefGoogle Scholar
  60. 60.
    Grinnell, F., Zhu, M., and Parks, W. C. (1997) Collagenase-1 complexes with a2-macroglobulin in the acute and chronic wound environments. J Invest Dermatol 110, 771-776.CrossRefGoogle Scholar
  61. 61.
    Chen, P., Farivar, A. S., Mulligan, M. S., and Madtes, D. K. (2006) Tissue inhibitor of metalloproteinase-1 deficiency abrogates obliterative airway disease after heterotopic tracheal transplantation. Am J Respir Cell Mol Biol 34, 464–472.PubMedCrossRefGoogle Scholar
  62. 62.
    Chen, P., McGuire, J., Kim, K.-H., Hackman, R., Chen, A., Parks, W., and Madtes, D. (2008) Tissue inhibitor of metalloproteinase-1 moderates airway re-epithelialization by regulating matrilysin activity. Am J Pathol 172, 1256–1270.PubMedCrossRefGoogle Scholar
  63. 63.
    Mohammed, F. F., Pennington, C. J., Kassiri, Z., Rubin, J. S., Soloway, P. D., Ruther, U., Edwards, D. R., and Khokha, R. (2005) Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF activation in murine liver regeneration. Hepatology 41, 857–867.PubMedCrossRefGoogle Scholar
  64. 64.
    Lijnen, H. R., Van Hoef, B., Vanlinthout, I., Verstreken, M., Rio, M. C., and Collen, D. (1999) Accelerated neointima formation after vascular injury in mice with stromelysin-3 (MMP-11) gene inactivation. Arterioscler Thromb Vasc Biol 19, 2863–2870.PubMedCrossRefGoogle Scholar
  65. 65.
    Silence, J., Collen, D., and Lijnen, H. R. (2002) Reduced atherosclerotic plaque but enhanced aneurysm formation in mice with inactivation of the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene. Circ Res 90, 897–903.PubMedCrossRefGoogle Scholar
  66. 66.
    Salonurmi, T., Parikka, M., Kontusaari, S., Pirila, E., Munaut, C., Salo, T., and Tryggvason, K. (2004) Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice. Cell Tissue Res 315, 27–37.PubMedCrossRefGoogle Scholar
  67. 67.
    Leco, K. J., Waterhouse, P., Sanchez, O. H., Gowing, K. L., Poole, A. R., Wakeham, A., Mak, T. W., and Khokha, R. (2001) Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3). J Clin Invest 108, 817–829.PubMedGoogle Scholar
  68. 68.
    Gill, S. E., Pape, M. C., Khokha, R., Watson, A. J., and Leco, K. J. (2003) A null mutation for tissue inhibitor of metalloproteinases-3 (Timp-3) impairs murine bronchiole branching morphogenesis. Dev Biol 261, 313–323.PubMedCrossRefGoogle Scholar
  69. 69.
    Martin, E. L., Moyer, B. Z., Pape, M. C., Starcher, B., Leco, K. J., and Veldhuizen, R. A. (2003) 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 285, L1222–L1232.PubMedGoogle Scholar
  70. 70.
    Kawamoto, H., Yasuda, O., Suzuki, T., Ozaki, T., Yotsui, T., Higuchi, M., Rakugi, H., Fukuo, K., Ogihara, T., and Maeda, N. (2006) Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction. Hypertens Res 29, 285–294.PubMedCrossRefGoogle Scholar
  71. 71.
    Gill, S. E., Pape, M. C., and Leco, K. J. (2006) Tissue inhibitor of metalloproteinases 3 regulates extracellular matrix – cell signaling during bronchiole branching morphogenesis. Dev Biol 298, 540–554.PubMedCrossRefGoogle Scholar
  72. 72.
    Fata, J. E., Leco, K. J., Voura, E. B., Yu, H. Y., Waterhouse, P., Murphy, G., Moorehead, R. A., and Khokha, R. (2001) Accelerated apoptosis in the Timp-3-deficient mammary gland. J Clin Invest 108, 831–841.PubMedGoogle Scholar
  73. 73.
    Fedak, P. W., Smookler, D. S., Kassiri, Z., Ohno, N., Leco, K. J., Verma, S., Mickle, D. A., Watson, K. L., Hojilla, C. V., Cruz, W., Weisel, R. D., Li, R. K., and Khokha, R. (2004) TIMP-3 deficiency leads to dilated cardiomyopathy. Circulation 110, 2401–2409.PubMedCrossRefGoogle Scholar
  74. 74.
    Mohan, M. J., Seaton, T., Mitchell, J., Howe, A., Blackburn, K., Burkhart, W., Moyer, M., Patel, I., Waitt, G. M., Becherer, J. D., Moss, M. L., and Milla, M. E. (2002) The tumor necrosis factor-alpha converting enzyme (TACE): a unique metalloproteinase with highly defined substrate selectivity. Biochemistry 41, 9462–9469.PubMedCrossRefGoogle Scholar
  75. 75.
    Mohammed, F. F., Smookler, D. S., Taylor, S. E., Fingleton, B., Kassiri, Z., Sanchez, O. H., English, J. L., Matrisian, L. M., Au, B., Yeh, W. C., and Khokha, R. (2004) Abnormal TNF activity in Timp3−/− mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet 36, 969–977.PubMedCrossRefGoogle Scholar
  76. 76.
    English, J. L., Kassiri, Z., Koskivirta, I., Atkinson, S. J., Di Grappa, M., Soloway, P. D., Nagase, H., Vuorio, E., Murphy, G., and Khokha, R. (2006) Individual Timp deficiencies differentially impact pro-MMP-2 activation. J Biol Chem 281, 10337–10346.PubMedCrossRefGoogle Scholar
  77. 77.
    Murphy, G., Knauper, V., Cowell, S., Hembry, R., Stanton, H., Butler, G., Freije, J., Pendas, A. M., and Lopez-Otin, C. (1999) Evaluation of some newer matrix metalloproteinases. Ann N Y Acad Sci 878, 25–39.PubMedCrossRefGoogle Scholar
  78. 78.
    Aoki, T., Kataoka, H., Moriwaki, T., Nozaki, K., and Hashimoto, N. (2007) Role of TIMP-1 and TIMP-2 in the progression of cerebral aneurysms. Stroke 38, 2337–2345.PubMedCrossRefGoogle Scholar
  79. 79.
    Ruangpanit, N., Price, J. T., Holmbeck, K., Birkedal-Hansen, H., Guenzler, V., Huang, X., Chan, D., Bateman, J. F., and Thompson, E. W. (2002) MT1-MMP-dependent and -independent regulation of gelatinase a activation in long-term, ascorbate-treated fibroblast cultures: regulation by fibrillar collagen. Exp Cell Res 272, 109–118.PubMedCrossRefGoogle Scholar
  80. 80.
    Corry, D. B., Rishi, K., Kanellis, J., Kiss, A., Song, L. Z., Xu, J., Feng, L., Werb, Z., and Kheradmand, F. (2002) Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency. Nat Immunol 3, 347–353.PubMedCrossRefGoogle Scholar
  81. 81.
    Itoh, T., Matsuda, H., Tanioka, M., Kuwabara, K., Itohara, S., and Suzuki, R. (2002) The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis. J Immunol 169, 2643–2647.PubMedGoogle Scholar
  82. 82.
    Kato, T., Kure, T., Chang, J. H., Gabison, E. E., Itoh, T., Itohara, S., and Azar, D. T. (2001) Diminished corneal angiogenesis in gelatinase A-deficient mice. FEBS Lett 508, 187–190.PubMedCrossRefGoogle Scholar
  83. 83.
    Ohno-Matsui, K., Uetama, T., Yoshida, T., Hayano, M., Itoh, T., Morita, I., and Mochizuki, M. (2003) Reduced retinal angiogenesis in MMP-2-deficient mice. Invest Ophthalmol Vis Sci 44, 5370–5375.PubMedCrossRefGoogle Scholar
  84. 84.
    Berglin, L., Sarman, S., van der Ploeg, I., Steen, B., Ming, Y., Itohara, S., Seregard, S., and Kvanta, A. (2003) Reduced choroidal neovascular membrane formation in matrix metalloproteinase-2-deficient mice. Invest Ophthalmol Vis Sci 44, 403–408.PubMedCrossRefGoogle Scholar
  85. 85.
    Holmbeck, K., Bianco, P., Caterina, J., Yamada, S., Kromer, M., Kuznetsov, S. A., Mankani, M., Robey, P. G., Poole, A. R., Pidoux, I., Ward, J. M., and Birkedal-Hansen, H. (1999) MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99, 81–92.PubMedCrossRefGoogle Scholar
  86. 86.
    Holmbeck, K., Bianco, P., Chrysovergis, K., Yamada, S., and Birkedal-Hansen, H. (2003) MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth. J Cell Biol 163, 661–671.PubMedCrossRefGoogle Scholar
  87. 87.
    Holmbeck, K., Bianco, P., Pidoux, I., Inoue, S., Billinghurst, R. C., Wu, W., Chrysovergis, K., Yamada, S., Birkedal-Hansen, H., and Poole, A. R. (2005) The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone. J Cell Sci 118, 147–156.PubMedCrossRefGoogle Scholar
  88. 88.
    Zhou, Z., Apte, S. S., Soininen, R., Cao, R., Baaklini, G. Y., Rauser, R. W., Wang, J., Cao, Y., and Tryggvason, K. (2000) Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci U S A 97, 4052–4057.PubMedCrossRefGoogle Scholar
  89. 89.
    Vaisar, T., Kassim, S. Y., Gomez, I. G., Green, P. S., Hargarten, S., Gough, P. J., Parks, W. C., Wilson, C. L., Raines, E. W., and Heinecke, J. W. 2009 MMP-9 sheds the β2 integrin subunit (CD18) from macrophages. Mol Cell Proteomics 8, 1044–1060.Google Scholar
  90. 90.
    Manicone, A. M., Birkland, T. P., Yang, Y., Betsuyaku, T., Lohi, J., Skerrett, S. J., and Parks, W. C. 2009 Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia. J Immunol 182, 3866–3876.Google Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Sean E. Gill
    • 1
  • Sean Y. Kassim
    • 1
  • Timothy P. Birkland
    • 1
  • William C. Parks
    • 1
  1. 1.Center for Lung BiologyUniversity of Washington School of MedicineSeattleUSA

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