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Gene Review

MMP1  -  matrix metallopeptidase 1 (interstitial...

Homo sapiens

Synonyms: CLG, CLGN, Fibroblast collagenase, Interstitial collagenase, MMP-1, ...
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Disease relevance of MMP1


Psychiatry related information on MMP1


High impact information on MMP1


Chemical compound and disease context of MMP1


Biological context of MMP1


Anatomical context of MMP1


Associations of MMP1 with chemical compounds

  • Inhibitors of protein kinase C, phosphatidyl inositol 3-OH kinase, and calmodulin-dependent protein kinase do not attenuate MMP1 promoter activation [1].
  • A single guanine insertion polymorphism (2G) in the MMP1 promoter creates an Ets binding site that causes high levels of transcription and correlates with risk for some malignancies [28].
  • In MDA-MB-231 cells, low concentrations of MMP1 protein were detected in medium from treated cells and was only significantly increased after 24 h but it was inhibited by cycloheximide [26].
  • Phorbol myristate acetate, known to induce protease activity in other endothelial cell populations, stimulated MMP1, MMP9, and TIMP1 secretion in both NDEC and PEDEC [29].
  • RESULTS: The glucocorticoids, dexamethasone, triamcinolone, and prednisolone, markedly decreased MMP1, MMP3, MMP13, TIMPI, and ferritin steady-state mRNA levels [30].

Physical interactions of MMP1

  • The in vitro angiogenic activity of VEGF(165) blocked in the VEGF(165).CTGF complex was reactivated to original levels after CTGF digestion of the complex with MMP-1, -3, and -13 [31].
  • It was suggested that G-Gly increased the number of vesicles containing MMP-1 and that MMP-1 interacted with CD147 to increase invasion [17].
  • The MMP-1/TIMP-1 complex level was measured by an enzyme-linked immunosorbent assay kit [32].
  • Our data highlight a new PPAR-gamma-dependent inhibitory mechanism on IL-1beta-mediated cartilage degradation occurring through DNA binding competition on the composite PPRE/AP1 site in the MMP1 promoter [33].
  • Analysis of the signal transduction leading to activation of the MMP-1 gene revealed the presence of an OSM-responsive element (OMRE) encompassing the AP-1 binding site and the signal transducer and activator of transcription (STAT) binding element, which mediate activation by OSM [34].

Enzymatic interactions of MMP1

  • MMP-2 cleaves at the same Gly-Ile/Leu bond in the collagen alpha chains as interstitial collagenases with kcat and Km values similar to that of MMP-1 [35].
  • Experiments with intact type II collagen as well as a synthetic peptide suggested that MMP-13 cleaved type II collagen at the same bond as MMP-1, but this was then followed by a secondary cleavage that removed three amino acids from the 1/4 fragment amino terminus [36].
  • Matrix metalloproteinase (MMP)-2 cleaves the 4 amino-terminal residues of the chemokine, stromal cell-derived factor (SDF)-1alpha, yielding a highly neurotoxic molecule, SDF(5-67), which fails to bind to its cognate receptor, CXCR4 [37].
  • In this report, we have inserted the cDNA encoding the signal and propeptide sequences of MT1-MMP (MT(1-109)) and the cDNA encoding propeptide-deleted mature MT1-MMP (MT delta pro) in expression vectors that were then transfected into matrix metalloproteinase-deficient COS-1 cells [38].
  • Several members of the matrix metalloproteinase family have been reported to cleave aggrecan in the interglobular domain between Asn-341 and Phe-342 [39].

Co-localisations of MMP1


Regulatory relationships of MMP1


Other interactions of MMP1


Analytical, diagnostic and therapeutic context of MMP1


  1. Fibroblast growth factor receptor signaling activates the human interstitial collagenase promoter via the bipartite Ets-AP1 element. Newberry, E.P., Willis, D., Latifi, T., Boudreaux, J.M., Towler, D.A. Mol. Endocrinol. (1997) [Pubmed]
  2. Haplotypes in matrix metalloproteinase gene cluster on chromosome 11q22 contribute to the risk of lung cancer development and progression. Sun, T., Gao, Y., Tan, W., Ma, S., Zhang, X., Wang, Y., Zhang, Q., Guo, Y., Zhao, D., Zeng, C., Lin, D. Clin. Cancer Res. (2006) [Pubmed]
  3. Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer. Wenham, R.M., Calingaert, B., Ali, S., McClean, K., Whitaker, R., Bentley, R., Lancaster, J.M., Schildkraut, J., Marks, J., Berchuck, A. J. Soc. Gynecol. Investig. (2003) [Pubmed]
  4. The function of the SNP in the MMP1 and MMP3 promoter in susceptibility to endometriosis in China. Shan, K., Ying, W., Jian-Hui, Z., Wei, G., Na, W., Yan, L. Mol. Hum. Reprod. (2005) [Pubmed]
  5. Matrix metalloproteinase single-nucleotide polymorphisms and haplotypes predict breast cancer progression. Hughes, S., Agbaje, O., Bowen, R.L., Holliday, D.L., Shaw, J.A., Duffy, S., Jones, J.L. Clin. Cancer Res. (2007) [Pubmed]
  6. Interaction between matrix metalloproteinase 3 and the epsilon4 allele of apolipoprotein E increases the risk of Alzheimer's disease in Finns. Saarela, M.S., Lehtimäki, T., Rinne, J.O., Hervonen, A., Jylhä, M., Röyttä, M., Ahonen, J.P., Mattila, K.M. Neurosci. Lett. (2004) [Pubmed]
  7. Matrix metalloproteinase profile in patients with Creuztfeldt-Jakob disease. Kettlun, A., Collados, L., García, L., Cartier, L.A., Wolf, M.E., Mosnaim, A.D., Valenzuela, M.A. International journal of clinical practice. (2003) [Pubmed]
  8. A third-generation matrix metalloproteinase (MMP) inhibitor (ONO-4817) combined with docetaxel suppresses progression of lung micrometastasis of MMP-expressing tumor cells in nude mice. Yamamoto, A., Yano, S., Shiraga, M., Ogawa, H., Goto, H., Miki, T., Zhang, H., Sone, S. Int. J. Cancer (2003) [Pubmed]
  9. Mononuclear phagocyte differentiation, activation, and viral infection regulate matrix metalloproteinase expression: implications for human immunodeficiency virus type 1-associated dementia. Ghorpade, A., Persidskaia, R., Suryadevara, R., Che, M., Liu, X.J., Persidsky, Y., Gendelman, H.E. J. Virol. (2001) [Pubmed]
  10. Alterations of gene expression in human neutrophils induced by smoking cessation. Morozumi, T., Kubota, T., Sugita, N., Itagaki, M., Yoshie, H. Journal of clinical periodontology. (2004) [Pubmed]
  11. Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Chang, S., Young, B.D., Li, S., Qi, X., Richardson, J.A., Olson, E.N. Cell (2006) [Pubmed]
  12. Forcing the third dimension. Boudreau, N., Weaver, V. Cell (2006) [Pubmed]
  13. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Boire, A., Covic, L., Agarwal, A., Jacques, S., Sherifi, S., Kuliopulos, A. Cell (2005) [Pubmed]
  14. Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Hotary, K.B., Allen, E.D., Brooks, P.C., Datta, N.S., Long, M.W., Weiss, S.J. Cell (2003) [Pubmed]
  15. Inhibition of angiogenesis and metastasis in two murine models by the matrix metalloproteinase inhibitor, BMS-275291. Naglich, J.G., Jure-Kunkel, M., Gupta, E., Fargnoli, J., Henderson, A.J., Lewin, A.C., Talbott, R., Baxter, A., Bird, J., Savopoulos, R., Wills, R., Kramer, R.A., Trail, P.A. Cancer Res. (2001) [Pubmed]
  16. Selective hydrolysis of triple-helical substrates by matrix metalloproteinase-2 and -9. Lauer-Fields, J.L., Sritharan, T., Stack, M.S., Nagase, H., Fields, G.B. J. Biol. Chem. (2003) [Pubmed]
  17. Glycine-extended gastrin induces matrix metalloproteinase-1- and -3-mediated invasion of human colon cancer cells through type I collagen gel and Matrigel. Baba, M., Itoh, K., Tatsuta, M. Int. J. Cancer (2004) [Pubmed]
  18. Phosphocitrate inhibits calcium hydroxyapatite induced mitogenesis and upregulation of matrix metalloproteinase-1, interleukin-1beta and cyclooxygenase-2 mRNA in human breast cancer cell lines. Cooke, M.M., McCarthy, G.M., Sallis, J.D., Morgan, M.P. Breast Cancer Res. Treat. (2003) [Pubmed]
  19. Tretinoin reverses upregulation of matrix metalloproteinase-13 in human keloid-derived fibroblasts. Uchida, G., Yoshimura, K., Kitano, Y., Okazaki, M., Harii, K. Exp. Dermatol. (2003) [Pubmed]
  20. 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]
  21. Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis. Ray, A., Kuroki, K., Cook, J.L., Bal, B.S., Kenter, K., Aust, G., Ray, B.K. Arthritis Rheum. (2003) [Pubmed]
  22. Human neutrophil lactoferrin trans-activates the matrix metalloproteinase 1 gene through stress-activated MAPK signaling modules. Oh, S.M., Hahm, D.H., Kim, I.H., Choi, S.Y. J. Biol. Chem. (2001) [Pubmed]
  23. LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway. Kunapuli, P., Kasyapa, C.S., Hawthorn, L., Cowell, J.K. J. Biol. Chem. (2004) [Pubmed]
  24. Activation of gelatinase A (72-kDa type IV collagenase) induced by monensin in normal human fibroblasts. Li, L., Akers, K., Eisen, A.Z., Seltzer, J.L. Exp. Cell Res. (1997) [Pubmed]
  25. Ets domain transcription factor PE1 suppresses human interstitial collagenase promoter activity by antagonizing protein-DNA interactions at a critical AP1 element. Bidder, M., Loewy, A.P., Latifi, T., Newberry, E.P., Ferguson, G., Willis, D.M., Towler, D.A. Biochemistry (2000) [Pubmed]
  26. Induction of metalloproteinase (MMP1) expression by epidermal growth factor (EGF) receptor stimulation and serum deprivation in human breast tumour cells. Nutt, J.E., Lunec, J. Eur. J. Cancer (1996) [Pubmed]
  27. Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression. Wang, F., Murrell, G.A., Wang, M.X. J. Orthop. Res. (2007) [Pubmed]
  28. Epstein-Barr virus latent membrane protein 1 induces the matrix metalloproteinase-1 promoter via an Ets binding site formed by a single nucleotide polymorphism: enhanced susceptibility to nasopharyngeal carcinoma. Kondo, S., Wakisaka, N., Schell, M.J., Horikawa, T., Sheen, T.S., Sato, H., Furukawa, M., Pagano, J.S., Yoshizaki, T. Int. J. Cancer (2005) [Pubmed]
  29. Preeclamptic decidual microvascular endothelial cells express lower levels of matrix metalloproteinase-1 than normals. Gallery, E.D., Campbell, S., Arkell, J., Nguyen, M., Jackson, C.J. Microvasc. Res. (1999) [Pubmed]
  30. Dose-dependent effects of corticosteroids on the expression of matrix-related genes in normal and cytokine-treated articular chondrocytes. Richardson, D.W., Dodge, G.R. Inflamm. Res. (2003) [Pubmed]
  31. Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. Hashimoto, G., Inoki, I., Fujii, Y., Aoki, T., Ikeda, E., Okada, Y. J. Biol. Chem. (2002) [Pubmed]
  32. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids of patients with temporomandibular joint osteoarthritis. Kanyama, M., Kuboki, T., Kojima, S., Fujisawa, T., Hattori, T., Takigawa, M., Yamashita, A. Journal of orofacial pain. (2000) [Pubmed]
  33. Peroxisome proliferator-activated receptor-gamma down-regulates chondrocyte matrix metalloproteinase-1 via a novel composite element. François, M., Richette, P., Tsagris, L., Raymondjean, M., Fulchignoni-Lataud, M.C., Forest, C., Savouret, J.F., Corvol, M.T. J. Biol. Chem. (2004) [Pubmed]
  34. The mitogen-activated protein kinase and JAK-STAT signaling pathways are required for an oncostatin M-responsive element-mediated activation of matrix metalloproteinase 1 gene expression. Korzus, E., Nagase, H., Rydell, R., Travis, J. J. Biol. Chem. (1997) [Pubmed]
  35. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. Aimes, R.T., Quigley, J.P. J. Biol. Chem. (1995) [Pubmed]
  36. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. Mitchell, P.G., Magna, H.A., Reeves, L.M., Lopresti-Morrow, L.L., Yocum, S.A., Rosner, P.J., Geoghegan, K.F., Hambor, J.E. J. Clin. Invest. (1996) [Pubmed]
  37. Proteolytic processing of SDF-1{alpha} reveals a change in receptor specificity mediating HIV-associated neurodegeneration. Vergote, D., Butler, G.S., Ooms, M., Cox, J.H., Silva, C., Hollenberg, M.D., Jhamandas, J.H., Overall, C.M., Power, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  38. The propeptide domain of membrane type 1-matrix metalloproteinase acts as an intramolecular chaperone when expressed in trans with the mature sequence in COS-1 cells. Cao, J., Hymowitz, M., Conner, C., Bahou, W.F., Zucker, S. J. Biol. Chem. (2000) [Pubmed]
  39. Quantification of a matrix metalloproteinase-generated aggrecan G1 fragment using monospecific anti-peptide serum. Lark, M.W., Williams, H., Hoernner, L.A., Weidner, J., Ayala, J.M., Harper, C.F., Christen, A., Olszewski, J., Konteatis, Z., Webber, R. Biochem. J. (1995) [Pubmed]
  40. Matrix metalloproteinase-1 produced by human CXCL12-stimulated natural killer cells. Goda, S., Inoue, H., Umehara, H., Miyaji, M., Nagano, Y., Harakawa, N., Imai, H., Lee, P., Macarthy, J.B., Ikeo, T., Domae, N., Shimizu, Y., Iida, J. Am. J. Pathol. (2006) [Pubmed]
  41. Identification and characterization of extracellular matrix metalloproteinase inducer in human endometrium during the menstrual cycle in vivo and in vitro. Noguchi, Y., Sato, T., Hirata, M., Hara, T., Ohama, K., Ito, A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  42. Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Wang, H., Keiser, J.A. Circ. Res. (1998) [Pubmed]
  43. Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. Ogata, Y., Enghild, J.J., Nagase, H. J. Biol. Chem. (1992) [Pubmed]
  44. Interferon-gamma differentially regulates monocyte matrix metalloproteinase-1 and -9 through tumor necrosis factor-alpha and caspase 8. Zhou, M., Zhang, Y., Ardans, J.A., Wahl, L.M. J. Biol. Chem. (2003) [Pubmed]
  45. Cyclooxygenase-2-derived E prostaglandins down-regulate matrix metalloproteinase-1 expression in fibroblast-like synoviocytes via inhibition of extracellular signal-regulated kinase activation. Pillinger, M.H., Rosenthal, P.B., Tolani, S.N., Apsel, B., Dinsell, V., Greenberg, J., Chan, E.S., Gomez, P.F., Abramson, S.B. J. Immunol. (2003) [Pubmed]
  46. Oncostatin M stimulates monocyte chemoattractant protein-1- and interleukin-1-induced matrix metalloproteinase-1 production by human synovial fibroblasts in vitro. Langdon, C., Leith, J., Smith, F., Richards, C.D. Arthritis Rheum. (1997) [Pubmed]
  47. Role of Wnt-5A in interleukin-1beta-induced matrix metalloproteinase expression in rabbit temporomandibular joint condylar chondrocytes. Ge, X., Ma, X., Meng, J., Zhang, C., Ma, K., Zhou, C. Arthritis Rheum. (2009) [Pubmed]
  48. p38 mitogen-activated protein kinase-dependent activation of protein phosphatases 1 and 2A inhibits MEK1 and MEK2 activity and collagenase 1 (MMP-1) gene expression. Westermarck, J., Li, S.P., Kallunki, T., Han, J., Kähäri, V.M. Mol. Cell. Biol. (2001) [Pubmed]
  49. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture? Schönbeck, U., Mach, F., Sukhova, G.K., Murphy, C., Bonnefoy, J.Y., Fabunmi, R.P., Libby, P. Circ. Res. (1997) [Pubmed]
  50. Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer. Michael, M., Babic, B., Khokha, R., Tsao, M., Ho, J., Pintilie, M., Leco, K., Chamberlain, D., Shepherd, F.A. J. Clin. Oncol. (1999) [Pubmed]
  51. Interleukin-6 released from fibroblasts is essential for up-regulation of matrix metalloproteinase-1 expression by U937 macrophages in coculture: cross-talking between fibroblasts and U937 macrophages exposed to high glucose. Sundararaj, K.P., Samuvel, D.J., Li, Y., Sanders, J.J., Lopes-Virella, M.F., Huang, Y. J. Biol. Chem. (2009) [Pubmed]
  52. Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis. Ferri, N., Carragher, N.O., Raines, E.W. Am. J. Pathol. (2004) [Pubmed]
  53. Rheumatoid synovial endothelial cells secrete decreased levels of tissue inhibitor of MMP (TIMP1). Jackson, C.J., Arkell, J., Nguyen, M. Ann. Rheum. Dis. (1998) [Pubmed]
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