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Gene Review

Mmp14  -  matrix metallopeptidase 14 (membrane...

Mus musculus

Synonyms: AI325305, MMP-14, MMP-X1, MT-MMP, MT-MMP 1, ...
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Disease relevance of Mmp14


High impact information on Mmp14

  • Herein, we demonstrate that the membrane-anchored metalloproteinase, MT1-MMP, coordinates adipocyte differentiation in vivo [6].
  • By contrast, within the context of the 3-dimensional (3-D) ECM, normal adipocyte maturation requires a burst in MT1-MMP-mediated proteolysis that modulates pericellular collagen rigidity in a fashion that controls adipogenesis [6].
  • MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components [4].
  • MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues [4].
  • MMPs directly regulate this process as invasion-incompetent cells penetrate fibrin barriers when transfected with the most potent fibrinolytic metalloproteinase identified in endothelium, membrane type-1 MMP (MT1-MMP) [7].

Chemical compound and disease context of Mmp14


Biological context of Mmp14

  • The matrix metalloproteinase-14 (MMP-14) gene is structurally distinct from other MMP genes and is co-expressed with the TIMP-2 gene during mouse embryogenesis [10].
  • The mouse MMP-14 protein is encoded by ten exons [10].
  • The structure of the exons encoding the catalytic domain and pro-domain of MMP-14 is distinct from previously described MMP genes, whereas the exons encoding the hemopexin-like domains are similar to those of most other MMP genes [10].
  • The novel C-terminal peptide domains of MMP-14 are encoded by a single large exon that also encodes the 3'-untranslated region [10].
  • These cells were transiently transfected with a plasmid vector expressing a luciferase reporter gene downstream of the mouse MT1-MMP promoter [1].

Anatomical context of Mmp14

  • Endothelial cells from lungs of 1-week-old Mmp14-/- mice show reduced migration and formation of three-dimensional structures on Matrigel [11].
  • Lung development in Mmp14-/- mice is arrested at the prealveolar stage with compensatory hyperinflation of immature saccules [11].
  • However, MT1-MMP-deleted fibroblasts circumvented this early deficiency and exhibited compensatory fibrin-invasive activity [12].
  • The decrease of TIMP-2 levels in conditioned media and the increase of MT1-MMP levels in plasma membrane were observed [13].
  • 5. Only MT1-MMP and to a lesser extent MMP2 were detected in the ureter bud [14].

Associations of Mmp14 with chemical compounds


Regulatory relationships of Mmp14

  • In contrast, by adulthood MMP-2-/- mice had normal alveolar size and structure, indicating normal alveolar development was not dependent on the ability of MT1-MMP to activate pro-MMP-2 [17].
  • CONCLUSIONS: MT1-MMP was detected and expressed to a greater extent in naive mice than MT2-MMP and MT3-MMP [18].
  • Consistent with these in vitro findings, MT1-MMP-deficient brain tissues display a marked reduction in mural cell density as well as abnormal vessel wall morphology similar to that reported in mice expressing PDGF-B or PDGFRbeta hypomorphic alleles [19].
  • In primary astrocyte cultures, MT1-MMP mRNA was upregulated by exogeneous tumor necrosis factor alpha [20].
  • Overexpression of non-phosphorylatable cofilin was sufficient to induce the expression of MT1-MMP and MMP2 in the beta3-negative M2Tbeta3 cells [21].
  • ConA inhibited both the gene and protein expression of G6PT, while overexpression of recombinant G6PT inhibited MT1-MMP-mediated pro-MMP-2 activation but could not rescue BMSC from ConA-induced cell necrosis [22].

Other interactions of Mmp14

  • Mmp14 and the gene for tissue inhibitor of metalloproteinases-2 (Timp2) show a temporally and spatially co-regulated expression during mouse development [10].
  • IGF-I treatment increased luciferase activity in the transfected cells by up to 10-fold and augmented endogenous MT1-MMP mRNA and protein synthesis by up to 2-3-fold, relative to controls [1].
  • Notably, three members of the matrix metalloproteinase (Mmp) gene family (Mmp10, Mmp13, and Mmp14) were consistently up-regulated in tumour tissue [23].
  • The gene expression and protein distribution of matrix metalloproteinase (MMP) -2, -9, membrane type-1 MMP (MT1-MMP), as well as of TIMP-1, -2, and -3 were analyzed during mouse molar development [24].
  • Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP) and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 rgulates pro-MMP-2 activation [25].
  • MT1-MMP-dependent dedifferentiation was mediated by the PDGF-BB-PDGFRbeta pathway in parallel with the proteolytic processing of the multifunctional LDL receptor-related protein LRP1 and the dynamic internalization of a PDGFRbeta-beta3-integrin-MT1-MMP-LRP1 multi-component complex [26].

Analytical, diagnostic and therapeutic context of Mmp14


  1. Type 1 insulin-like growth factor regulates MT1-MMP synthesis and tumor invasion via PI 3-kinase/Akt signaling. Zhang, D., Brodt, P. Oncogene (2003) [Pubmed]
  2. Temporal expression and activation of matrix metalloproteinases-2, -9, and membrane type 1-matrix metalloproteinase following acute hindlimb ischemia. Muhs, B.E., Plitas, G., Delgado, Y., Ianus, I., Shaw, J.P., Adelman, M.A., Lamparello, P., Shamamian, P., Gagne, P. J. Surg. Res. (2003) [Pubmed]
  3. Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. Ha, H.Y., Moon, H.B., Nam, M.S., Lee, J.W., Ryoo, Z.Y., Lee, T.H., Lee, K.K., So, B.J., Sato, H., Seiki, M., Yu, D.Y. Cancer Res. (2001) [Pubmed]
  4. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Holmbeck, K., Bianco, P., Caterina, J., Yamada, S., Kromer, M., Kuznetsov, S.A., Mankani, M., Robey, P.G., Poole, A.R., Pidoux, I., Ward, J.M., Birkedal-Hansen, H. Cell (1999) [Pubmed]
  5. Membrane-type 1 matrix metalloproteinase regulates macrophage-dependent elastolytic activity and aneurysm formation in vivo. Xiong, W., Knispel, R., MacTaggart, J., Greiner, T.C., Weiss, S.J., Baxter, B.T. J. Biol. Chem. (2009) [Pubmed]
  6. A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Chun, T.H., Hotary, K.B., Sabeh, F., Saltiel, A.R., Allen, E.D., Weiss, S.J. Cell (2006) [Pubmed]
  7. Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Hiraoka, N., Allen, E., Apel, I.J., Gyetko, M.R., Weiss, S.J. Cell (1998) [Pubmed]
  8. O-glycosylation regulates autolysis of cellular membrane type-1 matrix metalloproteinase (MT1-MMP). Remacle, A.G., Chekanov, A.V., Golubkov, V.S., Savinov, A.Y., Rozanov, D.V., Strongin, A.Y. J. Biol. Chem. (2006) [Pubmed]
  9. Early Increased MT1-MMP Expression and Late MMP-2 and MMP-9 Activity during Angiotensin II Induced Aneurysm Formation. Eagleton, M.J., Ballard, N., Lynch, E., Srivastava, S.D., Upchurch, G.R., Stanley, J.C. J. Surg. Res. (2006) [Pubmed]
  10. The matrix metalloproteinase-14 (MMP-14) gene is structurally distinct from other MMP genes and is co-expressed with the TIMP-2 gene during mouse embryogenesis. Apte, S.S., Fukai, N., Beier, D.R., Olsen, B.R. J. Biol. Chem. (1997) [Pubmed]
  11. Distinctive functions of membrane type 1 matrix-metalloprotease (MT1-MMP or MMP-14) in lung and submandibular gland development are independent of its role in pro-MMP-2 activation. Oblander, S.A., Zhou, Z., Gálvez, B.G., Starcher, B., Shannon, J.M., Durbeej, M., Arroyo, A.G., Tryggvason, K., Apte, S.S. Dev. Biol. (2005) [Pubmed]
  12. Matrix metalloproteinases (MMPs) regulate fibrin-invasive activity via MT1-MMP-dependent and -independent processes. Hotary, K.B., Yana, I., Sabeh, F., Li, X.Y., Holmbeck, K., Birkedal-Hansen, H., Allen, E.D., Hiraoka, N., Weiss, S.J. J. Exp. Med. (2002) [Pubmed]
  13. Group IB secretory phospholipase A2 promotes matrix metalloproteinase-2-mediated cell migration via the phosphatidylinositol 3-kinase and Akt pathway. Choi, Y.A., Lim, H.K., Kim, J.R., Lee, C.H., Kim, Y.J., Kang, S.S., Baek, S.H. J. Biol. Chem. (2004) [Pubmed]
  14. Expression of the type IV collagenase system during mouse kidney development and tubule segmentation. Legallicier, B., Trugnan, G., Murphy, G., Lelongt, B., Ronco, P. J. Am. Soc. Nephrol. (2001) [Pubmed]
  15. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways. Lund, L.R., Rømer, J., Thomasset, N., Solberg, H., Pyke, C., Bissell, M.J., Danø, K., Werb, Z. Development (1996) [Pubmed]
  16. Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. Philip, S., Kundu, G.C. J. Biol. Chem. (2003) [Pubmed]
  17. Membrane-type 1 matrix metalloproteinase is required for normal alveolar development. Atkinson, J.J., Holmbeck, K., Yamada, S., Birkedal-Hansen, H., Parks, W.C., Senior, R.M. Dev. Dyn. (2005) [Pubmed]
  18. Membrane-type matrix metalloproteinases in mice intracorneally infected with Pseudomonas aeruginosa. Dong, Z., Ghabrial, M., Katar, M., Fridman, R., Berk, R.S. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  19. An MT1-MMP-PDGF receptor-beta axis regulates mural cell investment of the microvasculature. Lehti, K., Allen, E., Birkedal-Hansen, H., Holmbeck, K., Miyake, Y., Chun, T.H., Weiss, S.J. Genes Dev. (2005) [Pubmed]
  20. Elevated expression of membrane type 1 metalloproteinase (MT1-MMP) in reactive astrocytes following neurodegeneration in mouse central nervous system. Rathke-Hartlieb, S., Budde, P., Ewert, S., Schlomann, U., Staege, M.S., Jockusch, H., Bartsch, J.W., Frey, J. FEBS Lett. (2000) [Pubmed]
  21. Alphavbeta3 integrin and cofilin modulate K1735 melanoma cell invasion. Dang, D., Bamburg, J.R., Ramos, D.M. Exp. Cell Res. (2006) [Pubmed]
  22. MT1-MMP down-regulates the glucose 6-phosphate transporter expression in marrow stromal cells: a molecular link between pro-MMP-2 activation, chemotaxis, and cell survival. Currie, J.C., Fortier, S., Sina, A., Galipeau, J., Cao, J., Annabi, B. J. Biol. Chem. (2007) [Pubmed]
  23. Expression profiling of murine intestinal adenomas reveals early deregulation of multiple matrix metalloproteinase (Mmp) genes. Martinez, C., Bhattacharya, S., Freeman, T., Churchman, M., Ilyas, M. J. Pathol. (2005) [Pubmed]
  24. Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during mouse molar tooth development. Yoshiba, N., Yoshiba, K., Stoetzel, C., Perrin-Schmitt, F., Cam, Y., Ruch, J.V., Lesot, H. Dev. Dyn. (2003) [Pubmed]
  25. Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP) and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 rgulates pro-MMP-2 activation. Zhao, H., Bernardo, M.M., Osenkowski, P., Sohail, A., Pei, D., Nagase, H., Kashiwagi, M., Soloway, P.D., DeClerck, Y.A., Fridman, R. J. Biol. Chem. (2004) [Pubmed]
  26. MT1-MMP promotes vascular smooth muscle dedifferentiation through LRP1 processing. Lehti, K., Rose, N.F., Valavaara, S., Weiss, S.J., Keski-Oja, J. J. Cell. Sci. (2009) [Pubmed]
  27. MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis. Kinoh, H., Sato, H., Tsunezuka, Y., Takino, T., Kawashima, A., Okada, Y., Seiki, M. J. Cell. Sci. (1996) [Pubmed]
  28. Experimental hindlimb ischemia increases neutrophil-mediated matrix metalloproteinase activity: a potential mechanism for lung injury after limb ischemia. Plitas, G., Gagne, P.J., Muhs, B.E., Ianus, I.A., Shaw, J.P., Beudjekian, M., Delgado, Y., Jacobowitz, G., Rockman, C., Shamamian, P. J. Am. Coll. Surg. (2003) [Pubmed]
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