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Gene Review

Mmp9  -  matrix metallopeptidase 9

Rattus norvegicus

Synonyms: 92 kDa gelatinase, 92 kDa type IV collagenase, GELB, Gelatinase B, MMP-9, ...
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Disease relevance of Mmp9


Psychiatry related information on Mmp9

  • In organotypic hippocampal cultures, which lack blood cell-mediated inflammation and extrinsic connections, a broad-spectrum inhibitor of MMPs (MMPI), but also a selective MMP-9 inhibitor, protect hippocampal neurons against KA-induced excitotoxicity [6].

High impact information on Mmp9

  • PMN depletion simultaneously reduced neutrophil infiltration and MMP-9 levels in lung tissue [7].
  • CONCLUSIONS: MMP-9 secretion by PMN can be stimulated by trypsin and proinflammatory cytokines and increases in pancreatitis in proportion to its severity [7].
  • Rat renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin-1 beta [8].
  • The addition of recombinant glutathione transferase-HuR prevented the rapid decay of MMP-9 mRNA, whereas the addition of a neutralizing anti-HuR antibody caused an acceleration of MMP-9 mRNA degradation [8].
  • We demonstrate that NO does strongly destabilize MMP-9 mRNA, since different luciferase reporter gene constructs containing the MMP-9 3' untranslated region (UTR) displayed significant reduced luciferase activity in response to the presence of NO [8].

Chemical compound and disease context of Mmp9


Biological context of Mmp9


Anatomical context of Mmp9


Associations of Mmp9 with chemical compounds

  • To elucidate transcriptional mechanisms for increased gelatinase B expression after hyperoxia, nuclear transcription factor-kappabeta activation was explored [18].
  • The Ras-induced increase in NF-kappaB DNA binding could be inhibited by treatment with the antioxidants N-acetyl-L-cysteine and glutathione monoester, suggesting that intracellular oxidant levels can mediate MMP-9 transcription [15].
  • Earlier, we showed that lipopolysaccharide (LPS) disrupted the BBB through the action of gelatinase B (MMP-9) [20].
  • Using zymography and semi-quantitative RT-PCR analysis, we showed that treatment of C6 cells with wortmannin, an inhibitor of PI 3-kinase activity, potentiated the expression of MMP-9 induced by both cytokines [5].
  • Protein levels of tTG and MMP-9 were also analyzed by Western blotting.In situtransglutaminase activity was assayed by measurement of incorporated substrate and the immunofluorescence staining for the cross-linking product, epsilon-(gamma-glutamyl) lysine [21].
  • As evidenced by MMP-9 promoter and electrophoretic mobility shift assays, ascofuranone specifically inhibited MMP-9 gene expression by blocking PMA-stimulated activation of activator protein-1 (AP-1) [22].

Physical interactions of Mmp9

  • Thus multiple pathways leading to activation of NFkappaB, SP-1, Ets, AP-1, and retinoblastoma binding factors in tumor cells all may contribute to MMP-9 transcription and hence to metastasis [23].

Enzymatic interactions of Mmp9

  • At 12 hours, tPA-treated rats showed significantly higher levels of pro-MMP-9 and cleaved MMP-9 than untreated controls [24].

Regulatory relationships of Mmp9


Other interactions of Mmp9

  • This effect was specific to MMP-2, because the closely related MMP-9 did not reproduce these changes [29].
  • RESULTS: MMP-9, MMP-13, and MMP-14 were expressed in discrete perichondrial cells that gave way to sites of intrachondral canal formation [30].
  • An important role of MMP-2, MMP-9, and TIMP-4 in hypertensive remodeling of the cortex and medulla in the SHR is demonstrated [31].
  • Induction of myofibroblast MMP-9 transcription in three-dimensional collagen I gel cultures: regulation by NF-kappaB, AP-1 and Sp1 [17].
  • Both MMP-9 and TIMP-3 were regulated by various cytokines [32].

Analytical, diagnostic and therapeutic context of Mmp9

  • We found that the proteolytic activities of MMP-2 and MMP-9 increased by 2 days after ligation, reached maximal levels at day 10, and remained high through the study period, whereas the gelatinolytic activities in plasma were unchanged [33].
  • Glomerular MMP-9 mRNA was reduced 4.6 +/- 0.6-fold (n = 3; p < 0.05), MMP-9 protein was not detectable by Western blotting and MMP-9 activity was considerably suppressed in gelatin zymograms [13].
  • Gel mobility shift assays demonstrated that Ras overexpression enhanced NF-kappaB, but not AP-1 DNA binding to motifs in the MMP-9 gene promoter [15].
  • Gelatin zymography and Northern blotting were used to confirm induction of MMP-9 protein and mRNA expression in primary rat HSC cultured in a three-dimensional collagen I gel lattice [17].
  • Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures [34].


  1. Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis. Kieseier, B.C., Kiefer, R., Clements, J.M., Miller, K., Wells, G.M., Schweitzer, T., Gearing, A.J., Hartung, H.P. Brain (1998) [Pubmed]
  2. Differential regulation of matrix metalloproteinase-2 and -9 expression and activity in adult rat cardiac fibroblasts in response to interleukin-1beta. Xie, Z., Singh, M., Singh, K. J. Biol. Chem. (2004) [Pubmed]
  3. Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. Rosenberg, G.A., Navratil, M., Barone, F., Feuerstein, G. J. Cereb. Blood Flow Metab. (1996) [Pubmed]
  4. Expression and activation of matrix metalloproteinase-2 and -9 in rat brain after transient focal cerebral ischemia. Planas, A.M., Solé, S., Justicia, C. Neurobiol. Dis. (2001) [Pubmed]
  5. Induced expression of MMP-9 in C6 glioma cells is inhibited by PDGF via a PI 3-kinase-dependent pathway. Estève, P.O., Robledo, O., Potworowski, E.F., St-Pierre, Y. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  6. Neuronal activity-dependent increase of net matrix metalloproteinase activity is associated with MMP-9 neurotoxicity after kainate. Jourquin, J., Tremblay, E., Décanis, N., Charton, G., Hanessian, S., Chollet, A.M., Le Diguardher, T., Khrestchatisky, M., Rivera, S. Eur. J. Neurosci. (2003) [Pubmed]
  7. Matrix metalloproteinase-9 promotes neutrophil migration and alveolar capillary leakage in pancreatitis-associated lung injury in the rat. Keck, T., Balcom, J.H., Fernández-del Castillo, C., Antoniu, B.A., Warshaw, A.L. Gastroenterology (2002) [Pubmed]
  8. Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR. Akool, e.l.-.S., Kleinert, H., Hamada, F.M., Abdelwahab, M.H., Förstermann, U., Pfeilschifter, J., Eberhardt, W. Mol. Cell. Biol. (2003) [Pubmed]
  9. Rat gastric gelatinase induction during endotoxemia. Robinson, E.K., West, S.D., Garay, A., Mercer, D.W. Dig. Dis. Sci. (2006) [Pubmed]
  10. TIMP-1/MMP-9 imbalance in brain edema in rats with fulminant hepatic failure. Yamamoto, S., Nguyen, J.H. J. Surg. Res. (2006) [Pubmed]
  11. Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer. Swarnakar, S., Ganguly, K., Kundu, P., Banerjee, A., Maity, P., Sharma, A.V. J. Biol. Chem. (2005) [Pubmed]
  12. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. Machado, L.S., Kozak, A., Ergul, A., Hess, D.C., Borlongan, C.V., Fagan, S.C. BMC neuroscience [electronic resource]. (2006) [Pubmed]
  13. Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats. Schaefer, L., Han, X., August, C., Matzkies, F., Lorenz, T., Schaefer, R.M. Diabetologia (1997) [Pubmed]
  14. Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Phillips, P.A., McCarroll, J.A., Park, S., Wu, M.J., Pirola, R., Korsten, M., Wilson, J.S., Apte, M.V. Gut (2003) [Pubmed]
  15. v-Ha-RaS oncogene upregulates the 92-kDa type IV collagenase (MMP-9) gene by increasing cellular superoxide production and activating NF-kappaB. Yang, J.Q., Zhao, W., Duan, H., Robbins, M.E., Buettner, G.R., Oberley, L.W., Domann, F.E. Free Radic. Biol. Med. (2001) [Pubmed]
  16. Transcription factor Ets-1 is essential for mesangial matrix remodeling. Mizui, M., Isaka, Y., Takabatake, Y., Sato, Y., Kawachi, H., Shimizu, F., Takahara, S., Ito, T., Imai, E. Kidney Int. (2006) [Pubmed]
  17. Induction of myofibroblast MMP-9 transcription in three-dimensional collagen I gel cultures: regulation by NF-kappaB, AP-1 and Sp1. Takahra, T., Smart, D.E., Oakley, F., Mann, D.A. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  18. Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia: pathogenetic implications. Pardo, A., Barrios, R., Maldonado, V., Meléndez, J., Pérez, J., Ruiz, V., Segura-Valdez, L., Sznajder, J.I., Selman, M. Am. J. Pathol. (1998) [Pubmed]
  19. Regulation of gelatinases in microglia and astrocyte cell cultures by plant lectins. Liuzzi, G.M., Santacroce, M.P., Peumans, W.J., Van Damme, E.J., Dubois, B., Opdenakker, G., Riccio, P. Glia (1999) [Pubmed]
  20. Stromelysin-1 and gelatinase A are upregulated before TNF-alpha in LPS-stimulated neuroinflammation. Mun-Bryce, S., Lukes, A., Wallace, J., Lukes-Marx, M., Rosenberg, G.A. Brain Res. (2002) [Pubmed]
  21. Increase in extracellular cross-linking by tissue transglutaminase and reduction in expression of MMP-9 contribute differentially to focal segmental glomerulosclerosis in rats. Liu, S., Li, Y., Zhao, H., Chen, D., Huang, Q., Wang, S., Zou, W., Zhang, Y., Li, X., Huang, H. Mol. Cell. Biochem. (2006) [Pubmed]
  22. Ascofuranone suppresses PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERK- and Ap1-dependent mechanisms. Cho, H.J., Kang, J.H., Kwak, J.Y., Lee, T.S., Lee, I.S., Park, N.G., Nakajima, H., Magae, J., Chang, Y.C. Carcinogenesis (2007) [Pubmed]
  23. Transcriptional activation of the matrix metalloproteinase-9 gene in an H-ras and v-myc transformed rat embryo cell line. Himelstein, B.P., Lee, E.J., Sato, H., Seiki, M., Muschel, R.J. Oncogene (1997) [Pubmed]
  24. Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats. Sumii, T., Lo, E.H. Stroke (2002) [Pubmed]
  25. Cytokine-mediated modulation of MMPs and TIMPs in multipotential neural precursor cells. Ben-Hur, T., Ben-Yosef, Y., Mizrachi-Kol, R., Ben-Menachem, O., Miller, A. J. Neuroimmunol. (2006) [Pubmed]
  26. Intracellular signalings underlying bradykinin-induced matrix metalloproteinase-9 expression in rat brain astrocyte-1. Hsieh, H.L., Yen, M.H., Jou, M.J., Yang, C.M. Cell. Signal. (2004) [Pubmed]
  27. ATP potentiates interleukin-1 beta-induced MMP-9 expression in mesangial cells via recruitment of the ELAV protein HuR. Huwiler, A., Akool, e.l.-.S., Aschrafi, A., Hamada, F.M., Pfeilschifter, J., Eberhardt, W. J. Biol. Chem. (2003) [Pubmed]
  28. TGF-beta increases retinal endothelial cell permeability by increasing MMP-9: possible role of glial cells in endothelial barrier function. Behzadian, M.A., Wang, X.L., Windsor, L.J., Ghaly, N., Caldwell, R.B. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  29. Matrix metalloproteinase 2 (gelatinase A) regulates glomerular mesangial cell proliferation and differentiation. Turck, J., Pollock, A.S., Lee, L.K., Marti, H.P., Lovett, D.H. J. Biol. Chem. (1996) [Pubmed]
  30. Expression patterns of matrix metalloproteinases and vascular endothelial growth factor during epiphyseal ossification. Alvarez, J., Costales, L., Serra, R., Balbín, M., López, J.M. J. Bone Miner. Res. (2005) [Pubmed]
  31. Mechanism of matrix accumulation and glomerulosclerosis in spontaneously hypertensive rats. Camp, T.M., Smiley, L.M., Hayden, M.R., Tyagi, S.C. J. Hypertens. (2003) [Pubmed]
  32. Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes. Muir, E.M., Adcock, K.H., Morgenstern, D.A., Clayton, R., von Stillfried, N., Rhodes, K., Ellis, C., Fawcett, J.W., Rogers, J.H. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  33. Altered balance between matrix metalloproteinases and their inhibitors in experimental biliary fibrosis. Kossakowska, A.E., Edwards, D.R., Lee, S.S., Urbanski, L.S., Stabbler, A.L., Zhang, C.L., Phillips, B.W., Zhang, Y., Urbanski, S.J. Am. J. Pathol. (1998) [Pubmed]
  34. Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures. Rosenberg, G.A., Cunningham, L.A., Wallace, J., Alexander, S., Estrada, E.Y., Grossetete, M., Razhagi, A., Miller, K., Gearing, A. Brain Res. (2001) [Pubmed]
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