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 (macrophage...

Homo sapiens

Synonyms: HME, ME, MME, MMP-12, Macrophage elastase, ...
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

  • Transgenic studies have shown that when MMP1 is over-expressed, pulmonary emphysema develops in mice, while MMP12 knockout mice do not develop pulmonary emphysema when exposed to cigarette smoke [1].
  • Both recombinant HME expressed in Escherichia coli and native HME derived from human alveolar macrophage-conditioned media degraded insoluble elastin [2].
  • On transcriptional assay by quantitative RT-PCR and real-time RT-PCR analysis to validate those molecules, both transcripts of MMP-10 and MMP-12 were significantly more upregulated in recurred stage IB lung cancer than in the non-recurred stage IB lung cancer (P=0.004) [3].
  • The MMP-12 structure is an excellent template for the structure-based design of specific inhibitors for emphysema therapy and for the construction of mutants to clarify the role of this MMP [4].
  • In contrast to other MMPs, overexpression of MMP-12 is associated with increased survival in colorectal cancer, presumably as a result of an inhibitory effect on angiogenesis [5].

Psychiatry related information on MMP12

  • The study took place at a freestanding sleep disorders center in Atlanta, Georgia, and two HME providers in Buffalo, New York, and Boston, Massachusetts. The patients comprised 21 adults who had been previously diagnosed with obstructive sleep apnea; there were 7 stable CPAP users with at least 1 year on therapy and 14 new users [6].

High impact information on MMP12


Chemical compound and disease context of MMP12

  • Using data from a population-based case-control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine [10].
  • When HME was incorporated into RBC ghosts by reversible hemolysis, the degree of inhibition of sodium efflux was comparable to that found with ouabain outside the red cells and was always greater than the inhibition produced with HME outside cells [11].
  • In this study, we report that the steroid extract 5alpha, 8alpha-epidioxycholest-6-ene-3beta-ol (MME) from Meretrix meretrix has the ability to inhibit growth of hepatoma cells and to induce G1-phase cell cycle arrest in two human hepatoma cell lines, HepG2 and Hep3B [12].
  • METHODS: 45 critically ill patients undergoing mechanical ventilation were included in the study and allocated to receive one of three humidification techniques: 1) Bennett Cascade water-bath humidifier (Bennett group); 2) Fisher & Paykel servocontrolled humidifier (F & P group); 3) HME Hygrobac DAR (HME group) [13].

Biological context of MMP12

  • However, haplotypes consisting of alleles from the MMP1 G-1607GG and MMP12 Asn357Ser polymorphisms were associated with rate of decline of lung function (P = 0.0007) [14].
  • Conversely, the SW480 transformants showed up-regulation of MMP12 and MMP17 [15].
  • In a Caucasian population, polymorphisms in the MMP1 and MMP12 genes, but not MMP9, have been suggested to be either causative factors in smoking-related lung injury or are in linkage disequilibrium with other causative polymorphisms [16].
  • HME and MME were similar in their substrate specificity and showed a stronger preference for Leu/Ile than did the 92-kDa enzyme [17].
  • The full-length HME cDNA spans 1.8 kilobases and contains an open reading frame of 1410 base pairs; the predicted molecular mass of the HME proenzyme is 54 kDa [2].

Anatomical context of MMP12

  • Migration of monocytes/macrophages in vitro and in vivo is accompanied by MMP12-dependent tunnel formation and by neovascularization [18].
  • Expression of MMP-12 by human macrophage cell lines was increased by stimulation with acetylated low-density lipoprotein, implying augmentation of MMP-12 production during foam cell formation [19].
  • HME mRNA and protein were detected in human alveolar macrophages [2].
  • The principal source of MMP-12 was macrophage foam cells (MFCs) that had infiltrated the atherosclerotic intima; this was demonstrated in both in vitro culture studies of MFCs purified from atherosclerotic lesions and immunohistochemical studies of aortic lesions [19].
  • In the atherosclerotic lesions, MMP-12 was produced abundantly at both the mRNA and protein levels, whereas no expression was observed in the normal rabbit aortas [19].

Associations of MMP12 with chemical compounds


Enzymatic interactions of MMP12

  • NH(2)-terminal amino acid sequencing revealed that MMP-12 cleaved TFPI at Lys(20)-Leu(21)(close to Kunitz I domain and producing a 35-kDa band), Arg(83)-Ile(84) (between Kunitz I and II domains), and Ser(174)-Thr(175) (between Kunitz II and III domains) [21].

Regulatory relationships of MMP12


Other interactions of MMP12

  • Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII [26].
  • Our results suggest that the abnormal production of tropoelastin and fibrillin by heat in human skin and that their degradation by various MMP, such as MMP-12, may contribute to the accumulation of elastotic material in photoaged skin [27].
  • MMP-7 (matrilysin) and MMP-12 (metalloelastase) were not found in either IPM or vitreous [28].
  • In MFS, decreased MMP-2 (76+/-7; P<0.05 versus control), increased MMP-12 (161+/-27% versus control; P<0.05), and increased MT1-MMP (248+/-64% versus 91+/-21 non-MFS and control; P<0.05) were observed [29].
  • RESULTS: We provide evidence that MMP-12 mRNA and protein are expressed by in-situ human airway smooth muscle cells obtained from bronchial biopsies of normal volunteers, and of patients with asthma, COPD and chronic cough [20].

Analytical, diagnostic and therapeutic context of MMP12


  1. Matrix metalloproteinases and TIMPs: properties and implications for the treatment of chronic obstructive pulmonary disease. Cawston, T., Carrere, S., Catterall, J., Duggleby, R., Elliott, S., Shingleton, B., Rowan, A. Novartis Found. Symp. (2001) [Pubmed]
  2. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. Shapiro, S.D., Kobayashi, D.K., Ley, T.J. J. Biol. Chem. (1993) [Pubmed]
  3. MMP expression profiling in recurred stage IB lung cancer. Cho, N.H., Hong, K.P., Hong, S.H., Kang, S., Chung, K.Y., Cho, S.H. Oncogene (2004) [Pubmed]
  4. Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure. Lang, R., Kocourek, A., Braun, M., Tschesche, H., Huber, R., Bode, W., Maskos, K. J. Mol. Biol. (2001) [Pubmed]
  5. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Zucker, S., Vacirca, J. Cancer Metastasis Rev. (2004) [Pubmed]
  6. Wireless CPAP patient monitoring: accuracy study. Lankford, D.A. Telemedicine journal and e-health : the official journal of the American Telemedicine Association. (2004) [Pubmed]
  7. Degradation of connective tissue matrices by macrophages. I. Proteolysis of elastin, glycoproteins, and collagen by proteinases isolated from macrophages. Werb, Z., Banda, M.J., Jones, P.A. J. Exp. Med. (1980) [Pubmed]
  8. Limited proteolysis by macrophage elastase inactivates human alpha 1-proteinase inhibitor. Banda, M.J., Clark, E.J., Werb, Z. J. Exp. Med. (1980) [Pubmed]
  9. Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms. Curci, J.A., Liao, S., Huffman, M.D., Shapiro, S.D., Thompson, R.W. J. Clin. Invest. (1998) [Pubmed]
  10. Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study. Shin, A., Cai, Q., Shu, X.O., Gao, Y.T., Zheng, W. Breast Cancer Res. (2005) [Pubmed]
  11. The effects of harmaline on sodium transport in human erythrocytes: evidence in favor of action at interior sodium-sensitive sites. Dunn, M.J., Hunt, W. J. Pharmacol. Exp. Ther. (1975) [Pubmed]
  12. Inhibition of cell growth and induction of G1-phase cell cycle arrest in hepatoma cells by steroid extract from Meretrix meretrix. Wu, T.H., Yang, R.L., Xie, L.P., Wang, H.Z., Chen, L., Zhang, S., Zhao, Y., Zhang, R.Q. Cancer Lett. (2006) [Pubmed]
  13. Comparison of three different humidification systems during prolonged mechanical ventilation. Luchetti, M., Stuani, A., Castelli, G., Marraro, G. Minerva anestesiologica. (1998) [Pubmed]
  14. The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Joos, L., He, J.Q., Shepherdson, M.B., Connett, J.E., Anthonisen, N.R., Paré, P.D., Sandford, A.J. Hum. Mol. Genet. (2002) [Pubmed]
  15. Overexpression of the thrombospondin 2 (TSP2) gene modulated by the matrix metalloproteinase family expression and production in human colon carcinoma cell line. Kamochi, J., Tokunaga, T., Tomii, Y., Abe, Y., Hatanaka, H., Kijima, H., Yamazaki, H., Watanabe, N., Matsuzaki, S., Ueyama, Y., Nakamura, M. Oncol. Rep. (2003) [Pubmed]
  16. Genetic polymorphisms of matrix metalloproteinases: functional importance in the development of chronic obstructive pulmonary disease? Wallace, A.M., Sandford, A.J. American journal of pharmacogenomics : genomics-related research in drug development and clinical practice. (2002) [Pubmed]
  17. Elastin degradation by matrix metalloproteinases. Cleavage site specificity and mechanisms of elastolysis. Mecham, R.P., Broekelmann, T.J., Fliszar, C.J., Shapiro, S.D., Welgus, H.G., Senior, R.M. J. Biol. Chem. (1997) [Pubmed]
  18. Migration of monocytes/macrophages in vitro and in vivo is accompanied by MMP12-dependent tunnel formation and by neovascularization. Anghelina, M., Schmeisser, A., Krishnan, P., Moldovan, L., Strasser, R.H., Moldovan, N.I. Cold Spring Harb. Symp. Quant. Biol. (2002) [Pubmed]
  19. Expression and localization of matrix metalloproteinase-12 in the aorta of cholesterol-fed rabbits: relationship to lesion development. Matsumoto, S., Kobayashi, T., Katoh, M., Saito, S., Ikeda, Y., Kobori, M., Masuho, Y., Watanabe, T. Am. J. Pathol. (1998) [Pubmed]
  20. Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells. Xie, S., Issa, R., Sukkar, M.B., Oltmanns, U., Bhavsar, P.K., Papi, A., Caramori, G., Adcock, I., Chung, K.F. Respir. Res. (2005) [Pubmed]
  21. Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation. Belaaouaj, A.A., Li, A., Wun, T.C., Welgus, H.G., Shapiro, S.D. J. Biol. Chem. (2000) [Pubmed]
  22. Metalloelastase (MMP-12) expression by tumour cells in squamous cell carcinoma of the vulva correlates with invasiveness, while that by macrophages predicts better outcome. Kerkelä, E., Ala-aho, R., Klemi, P., Grénman, S., Shapiro, S.D., Kähäri, V.M., Saarialho-Kere, U. J. Pathol. (2002) [Pubmed]
  23. Elevated MMP-12 protein levels in induced sputum from patients with COPD. Demedts, I.K., Morel-Montero, A., Lebecque, S., Pacheco, Y., Cataldo, D., Joos, G.F., Pauwels, R.A., Brusselle, G.G. Thorax (2006) [Pubmed]
  24. Tenascin-C stimulates glioma cell invasion through matrix metalloproteinase-12. Sarkar, S., Nuttall, R.K., Liu, S., Edwards, D.R., Yong, V.W. Cancer Res. (2006) [Pubmed]
  25. Human macrophage metalloelastase (MMP-12) expression is induced in chondrocytes during fetal development and malignant transformation. Kerkelä, E., Böhling, T., Herva, R., Uria, J.A., Saarialho-Kere, U. Bone (2001) [Pubmed]
  26. Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII. Hiller, O., Lichte, A., Oberpichler, A., Kocourek, A., Tschesche, H. J. Biol. Chem. (2000) [Pubmed]
  27. Heat modulation of tropoelastin, fibrillin-1, and matrix metalloproteinase-12 in human skin in vivo. Chen, Z., Seo, J.Y., Kim, Y.K., Lee, S.R., Kim, K.H., Cho, K.H., Eun, H.C., Chung, J.H. J. Invest. Dermatol. (2005) [Pubmed]
  28. Matrix metalloproteinases and metalloproteinase inhibitors in human interphotoreceptor matrix and vitreous. Plantner, J.J., Smine, A., Quinn, T.A. Curr. Eye Res. (1998) [Pubmed]
  29. Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with Marfan syndrome. Ikonomidis, J.S., Jones, J.A., Barbour, J.R., Stroud, R.E., Clark, L.L., Kaplan, B.S., Zeeshan, A., Bavaria, J.E., Gorman, J.H., Spinale, F.G., Gorman, R.C. Circulation (2006) [Pubmed]
  30. Overexpression of cathepsin F, matrix metalloproteinases 11 and 12 in cervical cancer. Vazquez-Ortiz, G., Pina-Sanchez, P., Vazquez, K., Duenas, A., Taja, L., Mendoza, P., Garcia, J.A., Salcedo, M. BMC Cancer (2005) [Pubmed]
WikiGenes - Universities