The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Mmp12  -  matrix metallopeptidase 12

Mus musculus

Synonyms: AV378681, MME, MMP-12, MMP12, Macrophage metalloelastase, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Mmp12

  • Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12 [1].
  • We have uncovered a pathway in which the loss of integrin-mediated activation of latent TGF-beta causes age-dependent pulmonary emphysema through alterations of macrophage Mmp12 expression [1].
  • In addition, deficiency of MMP-9 or MMP-12 protected apolipoprotein E-deficient mice against atherosclerotic media destruction and ectasia, mechanisms that implicate the involvement of these MMPs in aneurysm formation [2].
  • MMP-9 or MMP-12 deficiency conferred significant protection against transmedial elastin degradation and ectasia in the atherosclerotic media [2].
  • Interestingly, enzymatic activities of MMP-12 and of a new identified adipocyte-derived 30-kDa metalloproteinase are enhanced in obese adipose tissue fractions, demonstrating that MMP/TIMP balance is shifted toward increased matrix degradation in obesity [3].

High impact information on Mmp12

  • Successive passages (more than three) of cultures established from the tumors resulted in complete depletion of macrophages; steady-state MME mRNA, elastinolytic activity, and production of angiostatin (in the presence of plasminogen) were correspondingly reduced [4].
  • Smoke-exposed MME-/- mice that received monthly intratracheal instillations of monocyte chemoattractant protein-1 showed accumulation of alveolar macrophages but did not develop air space enlargement [5].
  • Thus, macrophage elastase is probably sufficient for the development of emphysema that results from chronic inhalation of cigarette smoke [5].
  • Degradation by macrophage elastase was limited to the heavy chain, resulting in products that did not compete for binding to the macrophage Fc receptor [6].
  • Mouse macrophage elastase, a metalloproteinase secreted by inflammatory macrophages, catalyzed the limited proteolysis of selected subclasses of mouse immunoglobulins, including monomeric IgG2a, IgG3, and some forms of IgG2b [6].

Chemical compound and disease context of Mmp12

  • CONCLUSION : The present study shows that MMP-12 deficiency has no significant effect on bleomycin-induced fibrosis [7].
  • A subcloned mouse mammary epithelial cell line (COMMA-D/MME) was cultured on Engelbreth-Holm-Swarm (EHS) tumor cell matrix with lactogenic hormones (insulin, cortisol, prolactin) to stimulate differentiation and challenged with growth factors to interpret the relationship between the signals for growth and differentiation [8].

Biological context of Mmp12

  • Conversely, lesion size and buried fibrous layers were reduced in apoE/MMP-12 double knockouts compared with controls, and double knockouts had increased smooth muscle cell and reduced macrophage content in the plaque, indicative of a stable plaque phenotype [9].
  • In summary, in early TMEV infection, MMP-3 and TIMP-1 mRNA upregulation might be directly virus-induced, whereas persistent TMEV infection directly or indirectly stimulated MMP-12 production in microglia/macrophages and astrocytes and might account for ongoing demyelination in TME [10].
  • Systemic glucocorticoid treatment, which is known to result in impaired wound healing, led to a nearly complete shut-off of MME expression [11].
  • In summary, while most of the MMPs and TIMPs studied seem to be involved in cell proliferation and migration, MMP-12 might be decisive for myelination [12].
  • MMP-12 mRNA was not detected in MMP-12 -/- mice, in conformity with their genotype [7].

Anatomical context of Mmp12

  • In contrast, microglia expressed only MMP-12 mRNA under basal conditions [13].
  • Indeed, the addition of IGF-1 normalized the lack of maturation of oligodendrocytes that occurred in cultures from MMP-12 null mice [14].
  • These MMPs partake in myelinogenesis because myelination in the corpus callosum of MMP-9 and/or MMP-12 null mice was deficient from postnatal days 7 to 14 compared with that of wild-type mice [14].
  • In reepithelialized wound tissue, MME transcripts were detected in deep layers of reconstituted dermis and seemed to cluster around vascular structures [11].
  • Collectively, our data indicate a novel function for MMP-12 in the process of airway eosinophil accumulation [15].

Associations of Mmp12 with chemical compounds

  • 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 [16].
  • Here we investigated fibrotic response to bleomycin in MMP-12 deficient mice [7].
  • This protection is mediated at least partially through inhibition of hyperoxia-induced synthesis and release of matrix metalloproteinase (MMP)-9 and MMP-12 by neutrophils and alveolar resident cells [17].
  • Both PMN influx and increased levels of DES/HP could be restored by administering MAC from MME(+/+) mice to MME-deficient mice and then exposing them to smoke [18].
  • MME(+/+) mice exposed to smoke showed elevations in PMN, DES, and HP, but no elevations were seen in MME-deficient mice [18].

Enzymatic interactions of Mmp12


Regulatory relationships of Mmp12


Other interactions of Mmp12


Analytical, diagnostic and therapeutic context of Mmp12


  1. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Morris, D.G., Huang, X., Kaminski, N., Wang, Y., Shapiro, S.D., Dolganov, G., Glick, A., Sheppard, D. Nature (2003) [Pubmed]
  2. Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth. Luttun, A., Lutgens, E., Manderveld, A., Maris, K., Collen, D., Carmeliet, P., Moons, L. Circulation (2004) [Pubmed]
  3. Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. Chavey, C., Mari, B., Monthouel, M.N., Bonnafous, S., Anglard, P., Van Obberghen, E., Tartare-Deckert, S. J. Biol. Chem. (2003) [Pubmed]
  4. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Dong, Z., Kumar, R., Yang, X., Fidler, I.J. Cell (1997) [Pubmed]
  5. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Hautamaki, R.D., Kobayashi, D.K., Senior, R.M., Shapiro, S.D. Science (1997) [Pubmed]
  6. Selective proteolysis of immunoglobulins by mouse macrophage elastase. Banda, M.J., Clark, E.J., Werb, Z. J. Exp. Med. (1983) [Pubmed]
  7. Macrophage metalloelastase (MMP-12) deficiency does not alter bleomycin-induced pulmonary fibrosis in mice. Manoury, B., Nenan, S., Guenon, I., Boichot, E., Planquois, J.M., Bertrand, C.P., Lagente, V. Journal of inflammation (London, England) (2006) [Pubmed]
  8. A mammary epithelial cell line is transiently stimulated towards milk lipid synthesis by lactogenic treatments. Gibson, C.A., Baumrucker, C.R. Comp. Biochem. Physiol. A Physiol. (1996) [Pubmed]
  9. 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]
  10. MMP-12, MMP-3, and TIMP-1 are markedly upregulated in chronic demyelinating theiler murine encephalomyelitis. Ulrich, R., Baumgärtner, W., Gerhauser, I., Seeliger, F., Haist, V., Deschl, U., Alldinger, S. J. Neuropathol. Exp. Neurol. (2006) [Pubmed]
  11. Matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) are differentially expressed during excisional skin wound repair. Madlener, M., Parks, W.C., Werner, S. Exp. Cell Res. (1998) [Pubmed]
  12. Matrix metalloproteinases and their inhibitors in the developing mouse brain and spinal cord: a reverse transcription quantitative polymerase chain reaction study. Ulrich, R., Gerhauser, I., Seeliger, F., Baumgärtner, W., Alldinger, S. Dev. Neurosci. (2005) [Pubmed]
  13. Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells. Crocker, S.J., Milner, R., Pham-Mitchell, N., Campbell, I.L. J. Neurochem. (2006) [Pubmed]
  14. Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and -12 null mice. Larsen, P.H., DaSilva, A.G., Conant, K., Yong, V.W. J. Neurosci. (2006) [Pubmed]
  15. Interleukin-13-dependent expression of matrix metalloproteinase-12 is required for the development of airway eosinophilia in mice. Pouladi, M.A., Robbins, C.S., Swirski, F.K., Cundall, M., McKenzie, A.N., Jordana, M., Shapiro, S.D., Stämpfli, M.R. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  16. 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]
  17. Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury. Lian, X., Qin, Y., Hossain, S.A., Yang, L., White, A., Xu, H., Shipley, J.M., Li, T., Senior, R.M., Du, H., Yan, C. J. Immunol. (2005) [Pubmed]
  18. Acute cigarette smoke-induced connective tissue breakdown requires both neutrophils and macrophage metalloelastase in mice. Churg, A., Zay, K., Shay, S., Xie, C., Shapiro, S.D., Hendricks, R., Wright, J.L. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  19. Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption. Hou, P., Troen, T., Ovejero, M.C., Kirkegaard, T., Andersen, T.L., Byrjalsen, I., Ferreras, M., Sato, T., Shapiro, S.D., Foged, N.T., Delaissé, J.M. Bone (2004) [Pubmed]
  20. Differential regulation of type IV collagenases and metalloelastase in murine macrophages by the synthetic bacterial lipopeptide JBT 3002. Kumar, R., Xie, K., Eue, I., Dong, Z., Killion, J.J., Fidler, I.J. Int. J. Immunopharmacol. (2000) [Pubmed]
  21. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. Lanone, S., Zheng, T., Zhu, Z., Liu, W., Lee, C.G., Ma, B., Chen, Q., Homer, R.J., Wang, J., Rabach, L.A., Rabach, M.E., Shipley, J.M., Shapiro, S.D., Senior, R.M., Elias, J.A. J. Clin. Invest. (2002) [Pubmed]
  22. Differential regulation of metalloelastase activity in murine peritoneal macrophages by granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor. Kumar, R., Dong, Z., Fidler, I.J. J. Immunol. (1996) [Pubmed]
  23. Neutral lipids and peroxisome proliferator-activated receptor-{gamma} control pulmonary gene expression and inflammation-triggered pathogenesis in lysosomal acid lipase knockout mice. Lian, X., Yan, C., Qin, Y., Knox, L., Li, T., Du, H. Am. J. Pathol. (2005) [Pubmed]
  24. Proteinase-activated receptor-1 regulation of macrophage elastase (MMP-12) secretion by serine proteinases. Raza, S.L., Nehring, L.C., Shapiro, S.D., Cornelius, L.A. J. Biol. Chem. (2000) [Pubmed]
  25. Impaired immunity to intestinal bacterial infection in stromelysin-1 (matrix metalloproteinase-3)-deficient mice. Li, C.K., Pender, S.L., Pickard, K.M., Chance, V., Holloway, J.A., Huett, A., Gonçalves, N.S., Mudgett, J.S., Dougan, G., Frankel, G., MacDonald, T.T. J. Immunol. (2004) [Pubmed]
  26. Surfactant protein-D regulates soluble CD14 through matrix metalloproteinase-12. Senft, A.P., Korfhagen, T.R., Whitsett, J.A., Shapiro, S.D., LeVine, A.M. J. Immunol. (2005) [Pubmed]
  27. Differential protease, innate immunity, and NF-{kappa}B induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice. Vlahos, R., Bozinovski, S., Jones, J.E., Powell, J., Gras, J., Lilja, A., Hansen, M.J., Gualano, R.C., Irving, L., Anderson, G.P. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  28. Expression of matrix metalloproteinases and their tissue inhibitor during viral encephalitis. Zhou, J., Marten, N.W., Bergmann, C.C., Macklin, W.B., Hinton, D.R., Stohlman, S.A. J. Virol. (2005) [Pubmed]
WikiGenes - Universities