Gene Symbol: Mmp12
Description: matrix metallopeptidase 12
Alias: AV378681, MME, Mmel, macrophage metalloelastase, macrophage elastase, matrix metalloproteinase 12
Species: mouse
Products:     Mmp12

Top Publications

  1. Fortino V, Maioli E, Torricelli C, Davis P, Valacchi G. Cutaneous MMPs are differently modulated by environmental stressors in old and young mice. Toxicol Lett. 2007;173:73-9 pubmed
    ..The current study demonstrates the ability of certain environmental pollutants to affect the ECM turnover through modulation of specific MMPs, and confirms the higher susceptibility of old subjects to exogenous pro-oxidant insults. ..
  2. Wells J, Rice T, Nuttall R, Edwards D, Zekki H, Rivest S, et al. An adverse role for matrix metalloproteinase 12 after spinal cord injury in mice. J Neurosci. 2003;23:10107-15 pubmed
    ..The data indicate that MMP-12 expression after spinal cord trauma is deleterious and contributes to the development of secondary injury in SCI. ..
  3. Matute Bello G, Wurfel M, Lee J, Park D, Frevert C, Madtes D, et al. Essential role of MMP-12 in Fas-induced lung fibrosis. Am J Respir Cell Mol Biol. 2007;37:210-21 pubmed
    ..and 7 showed sequential activation of co-regulated profibrotic genes, including marked up-regulation of matrix metalloproteinase 12 (MMP-12)...
  4. Dean R, Cox J, Bellac C, Doucet A, Starr A, Overall C. Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx. Blood. 2008;112:3455-64 pubmed publisher bronchoalveolar lavage fluid were significantly increased 72 hours after intranasal instillation of LPS in Mmp12(-/-) mice compared with wild type. Specificity occurred at 2 levels...
  5. Kassim S, Fu X, Liles W, Shapiro S, Parks W, Heinecke J. NADPH oxidase restrains the matrix metalloproteinase activity of macrophages. J Biol Chem. 2005;280:30201-5 pubmed
    ..These findings indicate that reactive intermediates provide a physiological mechanism to protect tissues from excessive macrophage-mediated damage during inflammation. ..
  6. Madala S, Pesce J, Ramalingam T, Wilson M, Minnicozzi S, Cheever A, et al. Matrix metalloproteinase 12-deficiency augments extracellular matrix degrading metalloproteinases and attenuates IL-13-dependent fibrosis. J Immunol. 2010;184:3955-63 pubmed publisher
    ..b>MMP12 is a macrophage-secreted elastase that is highly induced in the liver and lung in response to S...
  7. England K, Price A, Tram K, Shapiro S, Blazar B, Panoskaltsis Mortari A. Evidence for early fibrosis and increased airway resistance in bone marrow transplant recipient mice deficient in MMP12. Am J Physiol Lung Cell Mol Physiol. 2011;301:L519-26 pubmed publisher
    ..Because matrix metalloproteinase 12 (MMP12) is important for macrophage infiltration and injury in other mouse models of lung disease such ..
  8. Chan M, Li J, Bertrand A, Casbon A, Lin J, Maltseva I, et al. Protective effects of matrix metalloproteinase-12 following corneal injury. J Cell Sci. 2013;126:3948-60 pubmed publisher
    ..Here we demonstrate that the extracellular matrix metalloproteinase MMP12 (macrophage metalloelastase) is an important regulator of these repair processes...
  9. Warner R, Lewis C, Beltran L, Younkin E, Varani J, Johnson K. The role of metalloelastase in immune complex-induced acute lung injury. Am J Pathol. 2001;158:2139-44 pubmed
    ..Further, the data suggest that reduced injury in metalloelastase-deficient mice is due in part to decreased neutrophil influx into the alveolar space. ..

More Information


  1. Hautamaki R, Kobayashi D, Senior R, Shapiro S. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997;277:2002-4 pubmed
    ..determine which proteinases are responsible for the lung destruction characteristic of pulmonary emphysema, macrophage elastase-deficient (MME-/-) mice were subjected to cigarette smoke...
  2. Shipley J, Wesselschmidt R, Kobayashi D, Ley T, Shapiro S. Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci U S A. 1996;93:3942-6 pubmed
    ..We have eliminated expression of the macrophage metalloelastase (MME) gene by targeted disruption to assess the role of this protein in macrophage-mediated proteolysis...
  3. Shapiro S, Kobayashi D, Ley T. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem. 1993;268:23824-9 pubmed
    ..J. (1992) J. Biol. Chem. 267, 4664-4671). We now report that there is a human orthologue of murine macrophage metalloelastase that we call human macrophage metalloelastase (HME). The full-length HME cDNA spans 1...
  4. Kang H, Cho S, Lee C, Homer R, Elias J. Transforming growth factor (TGF)-beta1 stimulates pulmonary fibrosis and inflammation via a Bax-dependent, bid-activated pathway that involves matrix metalloproteinase-12. J Biol Chem. 2007;282:7723-32 pubmed
  5. Marchant D, Bellac C, Moraes T, Wadsworth S, Dufour A, Butler G, et al. A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity. Nat Med. 2014;20:493-502 pubmed publisher
    ..that activated I?B? mediates the export of IFN-? from virus-infected cells and that the inability of cells in Mmp12(-/-) but not wild-type mice to express I?B? and thus export IFN-? makes coxsackievirus type B3 infection lethal ..
  6. Wells J, Biernaskie J, Szymanska A, Larsen P, Yong V, Corbett D. Matrix metalloproteinase (MMP)-12 expression has a negative impact on sensorimotor function following intracerebral haemorrhage in mice. Eur J Neurosci. 2005;21:187-96 pubmed
    ..The data indicate that MMP-12 expression following haemorrhagic stroke is deleterious and contributes to the development of secondary injury in this disease. ..
  7. Longo G, Buda S, Fiotta N, Xiong W, Griener T, Shapiro S, et al. MMP-12 has a role in abdominal aortic aneurysms in mice. Surgery. 2005;137:457-62 pubmed
    ..MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment. ..
  8. Bozza M, Kolakowski L, Jenkins N, Gilbert D, Copeland N, David J, et al. Structural characterization and chromosomal location of the mouse macrophage migration inhibitory factor gene and pseudogenes. Genomics. 1995;27:412-9 pubmed
    ..Three of the Mif pseudogenes were also mapped by interspecific backcross to chromosomes 1, 9, and 17. These results suggest that Mif pseudogenes originated by retrotransposition. ..
  9. Nett M, Cerretti D, Berson D, Seavitt J, Gilbert D, Jenkins N, et al. Molecular cloning of the murine IL-1 beta converting enzyme cDNA. J Immunol. 1992;149:3254-9 pubmed
    ..These studies establish that the IL-1 beta convertase is an evolutionarily conserved, widely expressed enzyme that can be regulated at a pretranslational level. ..
  10. Edelstein C, Shapiro S, Klezovitch O, Scanu A. Macrophage metalloelastase, MMP-12, cleaves human apolipoprotein(a) in the linker region between kringles IV-4 and IV-5. Potential relevance to lipoprotein(a) biology. J Biol Chem. 1999;274:10019-23 pubmed
    In this study we found that macrophage metalloelastase, MMP-12 cleaves, in vitro, apolipoprotein(a) (apo(a)) in the Asn3518-Val3519 bond located in the linker region between kringles IV-4 and IV-5, a bond immediately upstream of the ..
  11. Li J, Wang J, Peng Q, Chen C, Humphrey M, Heinecke J, et al. Macrophage metalloelastase (MMP-12) deficiency mitigates retinal inflammation and pathological angiogenesis in ischemic retinopathy. PLoS ONE. 2012;7:e52699 pubmed publisher
    ..Recent evidence implicates macrophage metalloelastase (MMP-12), a macrophage-derived elastinolytic protease in inflammation, tissue remodeling and ..
  12. Wieslander C, Marinis S, Drewes P, Keller P, Acevedo J, Word R. Regulation of elastolytic proteases in the mouse vagina during pregnancy, parturition, and puerperium. Biol Reprod. 2008;78:521-8 pubmed
    ..the expression of matrix metalloproteases with elastase activity (matrix metalloproteinase [MMP] 2, MMP9, and MMP12) and their inhibitors in the vaginal wall of nonpregnant, pregnant, and postpartum mice...
  13. Houghton A, Hartzell W, Robbins C, Gomis Ruth F, Shapiro S. Macrophage elastase kills bacteria within murine macrophages. Nature. 2009;460:637-41 pubmed publisher
    ..Macrophage elastase (also known as matrix metalloproteinase 12 or MMP12) is an enzyme predominantly expressed in mature tissue macrophages and is implicated in ..
  14. Stawski L, Haines P, Fine A, Rudnicka L, Trojanowska M. MMP-12 deficiency attenuates angiotensin II-induced vascular injury, M2 macrophage accumulation, and skin and heart fibrosis. PLoS ONE. 2014;9:e109763 pubmed publisher
    ..Together, the results of this study show a close correlation between vascular injury markers, Arg 1+ macrophage accumulation and fibrosis and suggest an important role of MMP-12 in regulating these processes. ..
  15. Hartney J, Brown J, Chu H, Chang L, Pelanda R, Torres R. Arhgef1 regulates alpha5beta1 integrin-mediated matrix metalloproteinase expression and is required for homeostatic lung immunity. Am J Pathol. 2010;176:1157-68 pubmed publisher
    ..Together these data demonstrate that Arhgef1 regulates alpha5beta1-mediated MMP expression by macrophages and that loss of Arhgef1 by leukocytes leads to pulmonary pathology. ..
  16. Supasorn O, Sringkarin N, Srimanote P, Angkasekwinai P. Matrix metalloproteinases contribute to the regulation of chemokine expression and pulmonary inflammation in Cryptococcus infection. Clin Exp Immunol. 2016;183:431-40 pubmed publisher
    ..Among MMP family members, we found significant increases of MMP-3 and MMP-12 mRNA levels and MMP12 zymographic activities in response to C. neoformans but not C. gattii infection...
  17. Balbin M, Fueyo A, Knauper V, Lopez J, Alvarez J, Sanchez L, et al. Identification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation. J Biol Chem. 2001;276:10253-62 pubmed
  18. Lee Y, Fryer J, Kang H, Crespo Barreto J, Bowman A, Gao Y, et al. ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization. Dev Cell. 2011;21:746-57 pubmed publisher
    ..These findings demonstrate a critical role of ATXN1/ATXN1L-CIC complexes in extracellular matrix (ECM) remodeling during development and their potential roles in pathogenesis of disorders affecting ECM remodeling...
  19. Weaver A, Goncalves da Silva A, Nuttall R, Edwards D, Shapiro S, Rivest S, et al. An elevated matrix metalloproteinase (MMP) in an animal model of multiple sclerosis is protective by affecting Th1/Th2 polarization. FASEB J. 2005;19:1668-70 pubmed
    ..These results emphasize that specific MMPs can have beneficial roles in inflammation, and they implicate MMPs in T effector polarization for the first time. ..
  20. Houghton A, Grisolano J, Baumann M, Kobayashi D, Hautamaki R, Nehring L, et al. Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases. Cancer Res. 2006;66:6149-55 pubmed
    ..Here we show that mice deficient in macrophage elastase (MMP-12) develop significantly more gross Lewis lung carcinoma pulmonary metastases than their wild-type ..
  21. Dwivedi A, Slater S, George S. MMP-9 and -12 cause N-cadherin shedding and thereby beta-catenin signalling and vascular smooth muscle cell proliferation. Cardiovasc Res. 2009;81:178-86 pubmed publisher
    ..In conclusion, we propose that MMP-9 and -12 promote intimal thickening by independent cleavage of N-cadherin, which elevates VSMC proliferation via beta-catenin signalling. ..
  22. Nury C, Bregant S, Czarny B, Berthon F, Cassar Lajeunesse E, Dive V. Detection of endogenous matrix metalloprotease-12 active form with a novel broad spectrum activity-based probe. J Biol Chem. 2013;288:5636-44 pubmed publisher
    ..A less sensitive probe would therefore not have detected MMP-12. As the probe can detect other MMPs in the femtomolar range, it is a potentially powerful tool for monitoring the levels of MMP active forms in various diseases. ..
  23. Zang N, Zhuang J, Deng Y, Yang Z, Ye Z, Xie X, et al. Pulmonary C Fibers Modulate MMP-12 Production via PAR2 and Are Involved in the Long-Term Airway Inflammation and Airway Hyperresponsiveness Induced by Respiratory Syncytial Virus Infection. J Virol. 2015;90:2536-43 pubmed publisher
  24. Morris A, Kinnear G, Wan W, Wyss D, Bahra P, Stevenson C. Comparison of cigarette smoke-induced acute inflammation in multiple strains of mice and the effect of a matrix metalloproteinase inhibitor on these responses. J Pharmacol Exp Ther. 2008;327:851-62 pubmed publisher
    ..In addition, the ability of broad-spectrum MMP inhibitors to inhibit smoke-induced acute neutrophil inflammation is strain-dependent, whereas its ability to limit macrophage infiltration may be route dependent. ..
  25. Pellicoro A, Aucott R, Ramachandran P, Robson A, Fallowfield J, Snowdon V, et al. Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis. Hepatology. 2012;55:1965-75 pubmed publisher
    ..The aim of this work was to define elastin accumulation and the role of the paradigm elastase macrophage metalloelastase (MMP-12) in its turnover during fibrosis...
  26. Xu J, Tao B, Guo X, Zhou S, Li Y, Zhang Y, et al. Macrophage-Restricted Shp2 Tyrosine Phosphatase Acts as a Rheostat for MMP12 through TGF-? Activation in the Prevention of Age-Related Emphysema in Mice. J Immunol. 2017;199:2323-2332 pubmed publisher
    ..extracellular matrix degradation, and elevated levels of MMPs, particularly, significant increases of macrophage elastase (MMP12) in aged mice...
  27. Ma X, Tittiger M, Knutsen R, Kovacs A, Schaller L, Mecham R, et al. Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice. Mol Genet Metab. 2008;94:298-304 pubmed publisher
    ..This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders. ..
  28. Lanone S, Zheng T, Zhu Z, Liu W, Lee C, Ma B, et al. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. J Clin Invest. 2002;110:463-74 pubmed
    ..The also demonstrate that MMPs-9 and -12 play different roles in the generation of IL-13-induced inflammation, with MMP-9 inhibiting neutrophil accumulation and MMP-12 contributing to the accumulation of eosinophils and macrophages. ..
  29. Wang Y, Fang Z, Huang S, Cui L. [Tanshinone IIA down-regulates the expression of MMP-12 and TF in RAW 264.7 cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29:1317-20 pubmed
    ..TanIIA inhibits the cell proliferation and TF and MMP-12 expressions in RAW264.7 cells stimulated by ox-LDL, and these effects may be related with the anti-oxidation property of TanIIA. ..
  30. Wolf M, Maltseva I, Clay S, Pan P, Gajjala A, Chan M. Effects of MMP12 on cell motility and inflammation during corneal epithelial repair. Exp Eye Res. 2017;160:11-20 pubmed publisher
    ..We have previously shown that MMP12 has a protective effect on corneal fibrosis through its regulation of neutrophil and macrophage infiltration and ..
  31. Guyot R, Magre S, Leduque P, le Magueresse Battistoni B. Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1) during mouse gonad development. Dev Dyn. 2003;227:357-66 pubmed
    ..Experiments are now under way to determine to what extent TIMP-1 is a morphogenic gene involved in seminiferous cord formation and development. ..
  32. Zhou J, Stohlman S, Atkinson R, Hinton D, Marten N. Matrix metalloproteinase expression correlates with virulence following neurotropic mouse hepatitis virus infection. J Virol. 2002;76:7374-84 pubmed
    ..By contrast, MMP-9 protein activity was associated with the infiltration of neutrophils into the CNS. These data indicate an association between the magnitude of inflammatory gene expression within the CNS and viral virulence...
  33. Park J, Shin I, Ha U, Oh S, Kim J, Ahn K. Pathophysiological changes induced by Pseudomonas aeruginosa infection are involved in MMP-12 and MMP-13 upregulation in human carcinoma epithelial cells and a pneumonia mouse model. Infect Immun. 2015;83:4791-9 pubmed publisher
    ..Taken together, these data suggest that MMP-12 and MMP-13 alter strain K infection in mice and play a role in inflammatory regulation by modulating cytokine levels. ..
  34. Churg A, Dai J, Zay K, Karsan A, Hendricks R, Yee C, et al. Alpha-1-antitrypsin and a broad spectrum metalloprotease inhibitor, RS113456, have similar acute anti-inflammatory effects. Lab Invest. 2001;81:1119-31 pubmed
    ..also prevented the silica-induced acute inflammatory response in mice with knocked out genes for macrophage metalloelastase (MME -/-), mice that develop inflammation, but not connective tissue breakdown, and the pattern of ..
  35. Johnson J, Dwivedi A, Somerville M, George S, Newby A. Matrix metalloproteinase (MMP)-3 activates MMP-9 mediated vascular smooth muscle cell migration and neointima formation in mice. Arterioscler Thromb Vasc Biol. 2011;31:e35-44 pubmed publisher
    ..These findings add to the understanding of MMP action in plaque stability and restenosis. ..
  36. Johnson J, Devel L, Czarny B, George S, Jackson C, Rogakos V, et al. A selective matrix metalloproteinase-12 inhibitor retards atherosclerotic plaque development in apolipoprotein E-knockout mice. Arterioscler Thromb Vasc Biol. 2011;31:528-35 pubmed publisher
    ..Our study provides proof of principle to motivate translational work on MMP-12 inhibitor therapy in humans. ..
  37. Motterle A, Xiao Q, Kiechl S, Pender S, Morris G, Willeit J, et al. Influence of matrix metalloproteinase-12 on fibrinogen level. Atherosclerosis. 2012;220:351-4 pubmed publisher
    In vitro studies have shown that matrix metalloproteinase-12 (MMP12) can degrade fibrinogen, a clotting factor whose level predicts risk of advanced atherosclerosis and myocardial infarction...
  38. Wu Y, Li J, Wu J, Morgan P, Xu X, Rancati F, et al. Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD). Bioorg Med Chem Lett. 2012;22:138-43 pubmed publisher
    ..Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status. ..
  39. Newby A. Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation. Matrix Biol. 2015;44-46:157-66 pubmed publisher
    ..Overcoming these barriers would open the way to new treatments that could have a major impact on cardiovascular mortality worldwide. ..
  40. Liao G, Wang Z, Lee E, Moreno S, Abuelnasr O, Baudry M, et al. Enhanced expression of matrix metalloproteinase-12 contributes to Npc1 deficiency-induced axonal degeneration. Exp Neurol. 2015;269:67-74 pubmed publisher
    ..Our results indicate that abnormal neuronal expression of MMP-12 may contribute to axonal degeneration in NPC disease, thus providing a potential novel target for treatment. ..
  41. Zhang L, Ikegami M, Korfhagen T, McCormack F, Yoshida M, Senior R, et al. Neither SP-A nor NH2-terminal domains of SP-A can substitute for SP-D in regulation of alveolar homeostasis. Am J Physiol Lung Cell Mol Physiol. 2006;291:L181-90 pubmed
    ..Attempts to express rSftpd/a fusion protein in vivo were unsuccessful. Mmp9(-/-)/Sftpd(-/-) and Mmp12(-/-)/Sftpd(-/-) mice developed air space enlargement similar to Sftpd(-/-) mice, supporting the concept that the ..
  42. Takahashi S, Ishii M, Namkoong H, Hegab A, Asami T, Yagi K, et al. Pneumococcal Infection Aggravates Elastase-Induced Emphysema via Matrix Metalloproteinase 12 Overexpression. J Infect Dis. 2016;213:1018-30 pubmed publisher increased number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and increased matrix metalloproteinase 12 (MMP-12) production in the lungs, as well as enhanced emphysema progression...
  43. Marsland B, Kurrer M, Reissmann R, Harris N, Kopf M. Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages. Eur J Immunol. 2008;38:479-88 pubmed publisher
    ..Taken together, these data show that lung tissue damage caused by hookworm infection can result in the development of COPD and emphysema...
  44. Hu X, Li J, Zhang Q, Zheng L, Wang G, Zhang X, et al. Phosphoinositide 3-Kinase (PI3K) Subunit p110? Is Essential for Trophoblast Cell Differentiation and Placental Development in Mouse. Sci Rep. 2016;6:28201 pubmed publisher
    ..These data, taken together, provide the first in vivo evidence that p110? may play an important role in placental vascularization through manipulating trophoblast giant cell. ..
  45. Carmeliet P, Moons L, Lijnen R, Baes M, Lemaitre V, Tipping P, et al. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet. 1997;17:439-44 pubmed
  46. Gersten K, Natsuka S, Trinchera M, Petryniak B, Kelly R, Hiraiwa N, et al. Molecular cloning, expression, chromosomal assignment, and tissue-specific expression of a murine alpha-(1,3)-fucosyltransferase locus corresponding to the human ELAM-1 ligand fucosyl transferase. J Biol Chem. 1995;270:25047-56 pubmed
    ..Epithelial cell-specific expression of this gene suggests function(s) in addition to, and distinct from, its proposed role in selectin ligand synthesis. ..
  47. Acuff H, Sinnamon M, Fingleton B, Boone B, Levy S, Chen X, et al. Analysis of host- and tumor-derived proteinases using a custom dual species microarray reveals a protective role for stromal matrix metalloproteinase-12 in non-small cell lung cancer. Cancer Res. 2006;66:7968-75 pubmed
    ..The use of the Hu/Mu ProtIn chip allows us to distinguish tumor- and host-derived proteases and guides the further analysis of the significance of these genes in tumor progression. ..
  48. Shukla A, Barrett T, Nakayama K, Nakayama K, Mossman B, Lounsbury K. Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a PKCdelta-dependent pathway in murine lung. FASEB J. 2006;20:997-9 pubmed
    ..Asbestos-exposed PKCdelta knockout (PKCdelta-/-) mice exhibited decreased expression of lung MMP12 and MMP13 compared with asbestos-exposed wild-type mice...
  49. Goncalves Dasilva A, Liaw L, Yong V. Cleavage of osteopontin by matrix metalloproteinase-12 modulates experimental autoimmune encephalomyelitis disease in C57BL/6 mice. Am J Pathol. 2010;177:1448-58 pubmed publisher
    ..These results suggest that EAE disease activity may be modulated by the cleavage of OPN by MMP-12. ..
  50. DaSilva A, Yong V. Expression and regulation of matrix metalloproteinase-12 in experimental autoimmune encephalomyelitis and by bone marrow derived macrophages in vitro. J Neuroimmunol. 2008;199:24-34 pubmed publisher
    ..We postulate that cytokine - MMP-12 interactions are important in the disease process of EAE. ..
  51. Wang Y, Ait Oufella H, Herbin O, Bonnin P, Ramkhelawon B, Taleb S, et al. TGF-beta activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice. J Clin Invest. 2010;120:422-32 pubmed publisher
    ..These results clearly identify a critical role for TGF-beta in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome. ..
  52. Niu H, Li Y, Li H, Chi Y, Zhuang M, Zhang T, et al. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity. Sci Rep. 2016;6:20171 pubmed publisher
    ..These results suggest that regulating MMP-12 activity could be a therapeutic strategy for the treatment of crescentic glomerulonephritis and fibrogenesis. ..
  53. Lee M, Yoon B, Osiewicz K, Preston M, Bundy B, van Heeckeren A, et al. Tissue inhibitor of metalloproteinase 1 regulates resistance to infection. Infect Immun. 2005;73:661-5 pubmed
    ..Increased resistance was also seen during pulmonary infections. These results identify a novel pathway regulating infection resistance. ..
  54. Pyo R, Lee J, Shipley J, Curci J, Mao D, Ziporin S, et al. Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest. 2000;105:1641-9 pubmed
    ..Both 92-kD gelatinase (MMP-9) and macrophage elastase (MMP-12) have been implicated in this disease, but it is not known if either is necessary in aneurysmal ..
  55. Ogawa S, Lozach J, Jepsen K, Sawka Verhelle D, Perissi V, Sasik R, et al. A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation. Proc Natl Acad Sci U S A. 2004;101:14461-6 pubmed
  56. Long X, Li S, Xie J, Li W, Zang N, Ren L, et al. MMP-12-mediated by SARM-TRIF signaling pathway contributes to IFN-γ-independent airway inflammation and AHR post RSV infection in nude mice. Respir Res. 2015;16:11 pubmed publisher
    ..To the best of our knowledge, this study is the first that has examined the effects of SARM on MMP-12 and further highlights the potential to target SARM-TRIF-MMP-12 cascades to treat RSV infection. ..
  57. Vannella K, Barron L, Borthwick L, Kindrachuk K, Narasimhan P, Hart K, et al. Incomplete deletion of IL-4Rα by LysM(Cre) reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis. PLoS Pathog. 2014;10:e1004372 pubmed publisher
  58. Svedin P, Hagberg H, Mallard C. Expression of MMP-12 after neonatal hypoxic-ischemic brain injury in mice. Dev Neurosci. 2009;31:427-36 pubmed publisher
    ..This study demonstrates that MMP-12 is upregulated after HI, suggesting that MMP-12 may contribute to injury in the immature brain, similar to that seen in the adult. ..
  59. Nuttall R, Sampieri C, Pennington C, Gill S, Schultz G, Edwards D. Expression analysis of the entire MMP and TIMP gene families during mouse tissue development. FEBS Lett. 2004;563:129-34 pubmed
  60. Xu J, Xu F, Barrett E. Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice. Am J Physiol Lung Cell Mol Physiol. 2008;295:L162-70 pubmed publisher
    ..These findings suggest that SP has a modulatory effect on pulmonary MMP-12 by acting on NK1R to trigger MMP-12 syntheses in the AMs. ..
  61. Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, et al. Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice. Proc Natl Acad Sci U S A. 2005;102:15791-6 pubmed
    ..We propose that the lack of core fucosylation of TGF-beta1 receptors is crucial for a developmental and progressive/destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema. ..
  62. Liu Y, Zhang M, Hao W, Mihaljević I, Liu X, Xie K, et al. Matrix metalloproteinase-12 contributes to neuroinflammation in the aged brain. Neurobiol Aging. 2013;34:1231-9 pubmed publisher
    ..Thus, our study suggested that the upregulated cerebral MMP-12 during aging enhances aging-associated neuroinflammation by facilitating recruitment of bone marrow-derived microglia into the brain. ..
  63. Anghelina M, Schmeisser A, Krishnan P, Moldovan L, Strasser R, Moldovan N. Migration of monocytes/macrophages in vitro and in vivo is accompanied by MMP12-dependent tunnel formation and by neovascularization. Cold Spring Harb Symp Quant Biol. 2002;67:209-15 pubmed
  64. Qu P, Yan C, Du H. Matrix metalloproteinase 12 overexpression in myeloid lineage cells plays a key role in modulating myelopoiesis, immune suppression, and lung tumorigenesis. Blood. 2011;117:4476-89 pubmed publisher
    b>Matrix metalloproteinase 12 (MMP12) is a macrophage-secreting proteinase. To fully understand the function of MMP12 in myeloid lineage cells, a myeloid-specific c-fms-rtTA/(TetO)?-CMV-MMP12 bitransgenic mouse model was created...
  65. Trojanek J, Cobos Correa A, Diemer S, Kormann M, Schubert S, Zhou Suckow Z, et al. Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema. Am J Respir Cell Mol Biol. 2014;51:709-20 pubmed publisher
    ..We identified matrix metalloproteinase 12 (Mmp12) as a highly up-regulated gene in lungs from ?ENaC-Tg mice, and demonstrate that elevated Mmp12 ..
  66. Mizobe Y, Oikawa D, Tsuyama S, Akimoto Y, Hamasu K, Onitsuka E, et al. mRNA expression of lysyl oxidase and matrix metalloproteinase-12 in mouse skin. Biosci Biotechnol Biochem. 2008;72:3067-70 pubmed
    ..In contrast, higher MMP-12 mRNA expression was observed in the light period, suggesting that elastic fibers might be degraded in the light rather than the dark period. ..
  67. Johnson J, George S, Newby A, Jackson C. Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Proc Natl Acad Sci U S A. 2005;102:15575-80 pubmed
    ..These data demonstrate that MMPs are directly involved in atherosclerotic plaque destabilization and clearly show that members of the MMP family have widely differing effects on atherogenesis. ..
  68. Shapiro S, Goldstein N, Houghton A, Kobayashi D, Kelley D, Belaaouaj A. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol. 2003;163:2329-35 pubmed
    ..Previously, we demonstrated complete protection from emphysema in the absence of macrophage elastase. Further analysis revealed several interactions between these two elastases...
  69. Wei P, Tsai C, Chiu P, Lai S. Matrix metalloproteinase-12 leads to elastin degradation in BALB/c mice with eosinophilic meningitis caused by Angiostrongylus cantonensis. Int J Parasitol. 2011;41:1175-83 pubmed publisher
    ..These results imply that MMP-12 contributes to the elastin degradation that occurs in angiostrongyliasis meningitis, and doxycycline can reverse related inflammatory events by inhibition of MMP-12...
  70. Xu J, Xu F, Wang R, Seagrave J, Lin Y, March T. Cigarette smoke-induced hypercapnic emphysema in C3H mice is associated with increases of macrophage metalloelastase and substance P in the lungs. Exp Lung Res. 2007;33:197-215 pubmed
    The authors tested whether macrophage metalloelastase (MMP-12) and substance P (SP) were increased in the cigarette smoke (CS)-exposed female C3H/HeN mice with hypercapnic emphysema...
  71. Kim B, Abdel Rahman M, Wang T, Pouly S, Mahmoud A, Cebulla C. Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 expression in murine experimental retinal detachment. Invest Ophthalmol Vis Sci. 2014;55:2031-40 pubmed publisher
    ..Immunohistochemistry revealed moderate to strong MMP-13 levels in subretinal space macrophages. Fibrosis can develop in the HA-RD model. There is an upregulation of select MMPs that may modulate the wound healing process following RD. ..
  72. Kim S, Lee J, Cho W, Cho K, Sakong J, Kim J, et al. Role of NADPH oxidase-2 in lipopolysaccharide-induced matrix metalloproteinase expression and cell migration. Immunol Cell Biol. 2010;88:197-204 pubmed publisher
    ..MMP-9 expression and cell migration were controlled by ERK1/2-ROS signaling. Collectively, these results suggest that LPS stimulates ROS production via ERK and induce various types of MMPs expression and cell migration. ..
  73. Warner R, Lukacs N, Shapiro S, Bhagarvathula N, Nerusu K, Varani J, et al. Role of metalloelastase in a model of allergic lung responses induced by cockroach allergen. Am J Pathol. 2004;165:1921-30 pubmed
    ..Alterations in the levels of chemotactic factors and other proinflammatory cytokines in the MMP-12-deficient mice may underlie the decrease in leukocyte recruitment into inflamed lungs. ..
  74. Poobalasingam T, Yates L, Walker S, Pereira M, Gross N, Ali A, et al. Heterozygous Vangl2Looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair. Dis Model Mech. 2017;10:409-423 pubmed publisher
    ..altered macrophage population, abnormal elastin deposition and elevated levels of the elastin-modifying enzyme, Mmp12, all of which are observed in emphysema...
  75. Denis M, Cormier Y, Fournier M, Tardif J, Laviolette M. Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model. Am J Respir Cell Mol Biol. 1991;5:477-83 pubmed
    ..Anti-TNF-alpha also abolished lung index increases and lung fibrosis, with both parameters similar to that of saline-instilled mice.(ABSTRACT TRUNCATED AT 250 WORDS)..
  76. Kim M, Nepal S, Lee E, Jeong T, Kim S, Park P. Ethanol increases matrix metalloproteinase-12 expression via NADPH oxidase-dependent ROS production in macrophages. Toxicol Appl Pharmacol. 2013;273:77-89 pubmed publisher
    ..Taken together, these results demonstrate that ethanol treatment elicited increase in MMP-12 expression via increase in ROS production derived from Nox2 in macrophages. ..
  77. Liu S, Bae Y, Yu C, Monslow J, Hawthorne E, Castagnino P, et al. Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening. Sci Rep. 2015;5:17189 pubmed publisher
    ..Here we use mouse modeling to show that matrix metalloproteinase-12 (MMP12), a potent elastase, is essential for acute and chronic arterial stiffening...