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Gene Review

Mmp9  -  matrix metallopeptidase 9

Mus musculus

Synonyms: 92 kDa gelatinase, 92 kDa type IV collagenase, AW743869, B/MMP9, Clg4b, ...
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Disease relevance of Mmp9


Psychiatry related information on Mmp9

  • Activated MMP-9 (1 microg g(-1)) significantly prolonged the latency period of inducing platelet plug formation in mesenteric venules [5].
  • This study provides evidence that MMP-9 plays a key role in abnormal vascular permeability and inflammation within the first 3 d after spinal cord injury, and that blockade of MMPs during this critical period attenuates these vascular events and leads to improved locomotor recovery [6].

High impact information on Mmp9

  • BM ablation induces SDF-1, which upregulates MMP-9 expression, and causes shedding of sKitL and recruitment of c-Kit+ stem/progenitors [7].
  • Matrix metalloproteinase-9 (MMP-9), induced in BM cells, releases soluble Kit-ligand (sKitL), permitting the transfer of endothelial and hematopoietic stem cells (HSCs) from the quiescent to proliferative niche [7].
  • Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand [7].
  • Release of sKitL by MMP-9 enables BM repopulating cells to translocate to a permissive vascular niche favoring differentiation and reconstitution of the stem/progenitor cell pool [7].
  • In MMP-9-/- mice, release of sKitL and HSC motility are impaired, resulting in failure of hematopoietic recovery and increased mortality, while exogenous sKitL restores hematopoiesis and survival after BM ablation [7].

Chemical compound and disease context of Mmp9


Biological context of Mmp9


Anatomical context of Mmp9


Associations of Mmp9 with chemical compounds

  • They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9-dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-beta pathway [22].
  • Elastase-induced aneurysmal degeneration was suppressed by treatment with a nonselective MMP inhibitor (doxycycline) and by targeted gene disruption of MMP-9, but not by isolated deficiency of MMP-12 [2].
  • However, gelatinase B-deficient mice had a normal rate of resolution of acute inflammation elicited by cutaneous phenol [23].
  • Allergen exposure induced an increase of MMP-9-related gelatinolytic activity in WT lung extracts [24].
  • Proving the specificity of the effect, transient transfection of alphaT3-1 cells with ribozymes directed against MMP2 or MMP9 specifically blocked EGFR tyrosine phosphorylation in response to GnRH stimulation [25].
  • Overexpression of a dominant negative inhibitor of NF-kappaB or AP-1 blocked the TNF-alpha-induced expression of MMP-9 in myotubes [26].
  • M. avium-induced MMP-9 gene induction requires the histone acetyltransferase p300 and chromatin modifications involving phosphorylation of p65 at serine 276 and its acetylation at lysines 221 and 310 [27].

Physical interactions of Mmp9


Enzymatic interactions of Mmp9


Regulatory relationships of Mmp9


Other interactions of Mmp9

  • Excess NE produces lesions in GB -/- mice without cleaving alpha1-PI [1].
  • Instead, deficiency of urokinase-type plasminogen activator (u-PA-/-) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture [38].
  • TIMP-1 protected basement membrane type IV collagen from degradation by exogenous gelatinase B in cryostat sections of nerve in vitro [19].
  • A marked decrease in matrix metalloproteinase-9 (MMP-9) induction was found in the obstructed kidneys of tPA(-/-) mice, which led to a dramatic preservation of the structural and functional integrity of tubular basement membrane (TBM) [39].
  • Brachiocephalic artery plaques were significantly larger in apoE/MMP-3 and apoE/MMP-9 double knockouts than in controls [40].

Analytical, diagnostic and therapeutic context of Mmp9


  1. The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo. Liu, Z., Zhou, X., Shapiro, S.D., Shipley, J.M., Twining, S.S., Diaz, L.A., Senior, R.M., Werb, Z. Cell (2000) [Pubmed]
  2. Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. Pyo, R., Lee, J.K., Shipley, J.M., Curci, J.A., Mao, D., Ziporin, S.J., Ennis, T.L., Shapiro, S.D., Senior, R.M., Thompson, R.W. J. Clin. Invest. (2000) [Pubmed]
  3. Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. Ducharme, A., Frantz, S., Aikawa, M., Rabkin, E., Lindsey, M., Rohde, L.E., Schoen, F.J., Kelly, R.A., Werb, Z., Libby, P., Lee, R.T. J. Clin. Invest. (2000) [Pubmed]
  4. Synergy between a plasminogen cascade and MMP-9 in autoimmune disease. Liu, Z., Li, N., Diaz, L.A., Shipley, M., Senior, R.M., Werb, Z. J. Clin. Invest. (2005) [Pubmed]
  5. Expression of matrix metalloproteinase-9 in human platelets: regulation of platelet activation in in vitro and in vivo studies. Sheu, J.R., Fong, T.H., Liu, C.M., Shen, M.Y., Chen, T.L., Chang, Y., Lu, M.S., Hsiao, G. Br. J. Pharmacol. (2004) [Pubmed]
  6. Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. Noble, L.J., Donovan, F., Igarashi, T., Goussev, S., Werb, Z. J. Neurosci. (2002) [Pubmed]
  7. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N.R., Crystal, R.G., Besmer, P., Lyden, D., Moore, M.A., Werb, Z., Rafii, S. Cell (2002) [Pubmed]
  8. Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. Bruemmer, D., Collins, A.R., Noh, G., Wang, W., Territo, M., Arias-Magallona, S., Fishbein, M.C., Blaschke, F., Kintscher, U., Graf, K., Law, R.E., Hsueh, W.A. J. Clin. Invest. (2003) [Pubmed]
  9. In vivo activation of gelatinase B/MMP-9 by trypsin in acute pancreatitis is a permissive factor in streptozotocin-induced diabetes. Descamps, F.J., Martens, E., Ballaux, F., Geboes, K., Opdenakker, G. J. Pathol. (2004) [Pubmed]
  10. Essential role of endogenous tissue plasminogen activator through matrix metalloproteinase 9 induction and expression on heparin-produced cerebral hemorrhage after cerebral ischemia in mice. Zhao, B.Q., Ikeda, Y., Ihara, H., Urano, T., Fan, W., Mikawa, S., Suzuki, Y., Kondo, K., Sato, K., Nagai, N., Umemura, K. Blood (2004) [Pubmed]
  11. Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice. Lim, D.H., Cho, J.Y., Miller, M., McElwain, K., McElwain, S., Broide, D.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  12. Experimental hindlimb ischemia leads to neutrophil-mediated increases in gastrocnemius MMP-2 and -9 activity: a potential mechanism for ischemia induced MMP activation. Muhs, B.E., Gagne, P., Plitas, G., Shaw, J.P., Shamamian, P. J. Surg. Res. (2004) [Pubmed]
  13. Matrix metalloproteinase-9 maps to the distal end of chromosome 2 in the mouse. Leco, K.J., Harvey, M.B., Hogan, A., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Edwards, D.R., Schultz, G.A. Dev. Genet. (1997) [Pubmed]
  14. Assignment of matrix metalloproteinase 9 (Mmp9) to mouse chromosome 2 bands H1-H2. DuPont, B.R., Linn, R., Knight, C.B., Roodman, G.D., Sakaguchi, A.Y., Lalley, P.A., Fournier, R.E., Leach, R.J. Cytogenet. Cell Genet. (1996) [Pubmed]
  15. Defective trophoblast function in mice with a targeted mutation of Ets2. Yamamoto, H., Flannery, M.L., Kupriyanov, S., Pearce, J., McKercher, S.R., Henkel, G.W., Maki, R.A., Werb, Z., Oshima, R.G. Genes Dev. (1998) [Pubmed]
  16. Stromelysin-1 (MMP-3)-independent gelatinase expression and activation in mice. Lijnen, H.R., Silence, J., Van Hoef, B., Collen, D. Blood (1998) [Pubmed]
  17. Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice. Olle, E.W., Ren, X., McClintock, S.D., Warner, R.L., Deogracias, M.P., Johnson, K.J., Colletti, L.M. Hepatology (2006) [Pubmed]
  18. Role of neutrophils in matrix metalloproteinase activity in the preimplantation mouse uterus. Daimon, E., Wada, Y. Biol. Reprod. (2005) [Pubmed]
  19. Basement membrane and repair of injury to peripheral nerve: defining a potential role for macrophages, matrix metalloproteinases, and tissue inhibitor of metalloproteinases-1. La Fleur, M., Underwood, J.L., Rappolee, D.A., Werb, Z. J. Exp. Med. (1996) [Pubmed]
  20. Gelatinase B-deficient mice are resistant to experimental bullous pemphigoid. Liu, Z., Shipley, J.M., Vu, T.H., Zhou, X., Diaz, L.A., Werb, Z., Senior, R.M. J. Exp. Med. (1998) [Pubmed]
  21. A role for focal adhesion kinase signaling in tumor necrosis factor-alpha-dependent matrix metalloproteinase-9 production in a cholangiocarcinoma cell line, CCKS1. Mon, N.N., Hasegawa, H., Thant, A.A., Huang, P., Tanimura, Y., Senga, T., Hamaguchi, M. Cancer Res. (2006) [Pubmed]
  22. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). Lee, C.G., Homer, R.J., Zhu, Z., Lanone, S., Wang, X., Koteliansky, V., Shipley, J.M., Gotwals, P., Noble, P., Chen, Q., Senior, R.M., Elias, J.A. J. Exp. Med. (2001) [Pubmed]
  23. Matrix metalloproteinase deficiencies affect contact hypersensitivity: stromelysin-1 deficiency prevents the response and gelatinase B deficiency prolongs the response. Wang, M., Qin, X., Mudgett, J.S., Ferguson, T.A., Senior, R.M., Welgus, H.G. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  24. Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation. Cataldo, D.D., Tournoy, K.G., Vermaelen, K., Munaut, C., Foidart, J.M., Louis, R., Noël, A., Pauwels, R.A. Am. J. Pathol. (2002) [Pubmed]
  25. Matrix metalloproteinases 2 and 9 mediate epidermal growth factor receptor transactivation by gonadotropin-releasing hormone. Roelle, S., Grosse, R., Aigner, A., Krell, H.W., Czubayko, F., Gudermann, T. J. Biol. Chem. (2003) [Pubmed]
  26. Tumor necrosis factor-alpha augments matrix metalloproteinase-9 production in skeletal muscle cells through the activation of transforming growth factor-beta-activated kinase 1 (TAK1)-dependent signaling pathway. Srivastava, A.K., Qin, X., Wedhas, N., Arnush, M., Linkhart, T.A., Chadwick, R.B., Kumar, A. J. Biol. Chem. (2007) [Pubmed]
  27. Mycobacterium avium-induced matrix metalloproteinase-9 expression occurs in a cyclooxygenase-2-dependent manner and involves phosphorylation- and acetylation-dependent chromatin modification. Basu, S., Pathak, S., Pathak, S.K., Bhattacharyya, A., Banerjee, A., Kundu, M., Basu, J. Cell. Microbiol. (2007) [Pubmed]
  28. Transcription Factors Pax6 and AP-2alpha Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B. Sivak, J.M., West-Mays, J.A., Yee, A., Williams, T., Fini, M.E. Mol. Cell. Biol. (2004) [Pubmed]
  29. Structure-function studies on the biosynthesis and bioactivity of the precursor convertase PC2 and the formation of the PC2/7B2 complex. Benjannet, S., Lusson, J., Hamelin, J., Savaria, D., Chrétien, M., Seidah, N.G. FEBS Lett. (1995) [Pubmed]
  30. Activation of hepatocyte growth factor (HGF) by endogenous HGF activator is required for metanephric kidney morphogenesis in vitro. van Adelsberg, J., Sehgal, S., Kukes, A., Brady, C., Barasch, J., Yang, J., Huan, Y. J. Biol. Chem. (2001) [Pubmed]
  31. The selective increase in caspase-3 expression in effector but not memory T cells allows susceptibility to apoptosis. Sabbagh, L., Kaech, S.M., Bourbonnière, M., Woo, M., Cohen, L.Y., Haddad, E.K., Labrecque, N., Ahmed, R., Sékaly, R.P. J. Immunol. (2004) [Pubmed]
  32. Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein. Gijbels, K., Proost, P., Masure, S., Carton, H., Billiau, A., Opdenakker, G. J. Neurosci. Res. (1993) [Pubmed]
  33. Involvement of transforming growth factor beta1 in autocrine enhancement of gelatinase B secretion by murine metastatic colon carcinoma cells. Shimizu, S., Nishikawa, Y., Kuroda, K., Takagi, S., Kozaki, K., Hyuga, S., Saga, S., Matsuyama, M. Cancer Res. (1996) [Pubmed]
  34. Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression. Hu, K., Yang, J., Tanaka, S., Gonias, S.L., Mars, W.M., Liu, Y. J. Biol. Chem. (2006) [Pubmed]
  35. Nuclear factor-inducing kinase plays a crucial role in osteopontin-induced MAPK/IkappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation. Rangaswami, H., Bulbule, A., Kundu, G.C. J. Biol. Chem. (2004) [Pubmed]
  36. Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. Tang, J., Liu, J., Zhou, C., Alexander, J.S., Nanda, A., Granger, D.N., Zhang, J.H. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  37. Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease. Lau, A.C., Duong, T.T., Ito, S., Yeung, R.S. Arthritis Rheum. (2008) [Pubmed]
  38. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Heymans, S., Luttun, A., Nuyens, D., Theilmeier, G., Creemers, E., Moons, L., Dyspersin, G.D., Cleutjens, J.P., Shipley, M., Angellilo, A., Levi, M., Nübe, O., Baker, A., Keshet, E., Lupu, F., Herbert, J.M., Smits, J.F., Shapiro, S.D., Baes, M., Borgers, M., Collen, D., Daemen, M.J., Carmeliet, P. Nat. Med. (1999) [Pubmed]
  39. Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy. Yang, J., Shultz, R.W., Mars, W.M., Wegner, R.E., Li, Y., Dai, C., Nejak, K., Liu, Y. J. Clin. Invest. (2002) [Pubmed]
  40. Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Johnson, J.L., George, S.J., Newby, A.C., Jackson, C.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  41. Cag Pathogenicity Island-independent Up-regulation of Matrix Metalloproteinases-9 and -2 Secretion and Expression in Mice by Helicobacter pylori Infection. Kundu, P., Mukhopadhyay, A.K., Patra, R., Banerjee, A., Berg, D.E., Swarnakar, S. J. Biol. Chem. (2006) [Pubmed]
  42. Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury. Rosenberg, G.A., Dencoff, J.E., Correa, N., Reiners, M., Ford, C.C. Neurology (1996) [Pubmed]
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