Matrix Metalloproteinase-2 (MMP-2)
Matrix Metalloproteinase-2 (MMP-2), also known as 72kd type IV collagenase, is a ubiquitous metalloproteinase that is involved in diverse functions including remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. MMP-2 is also involved in degrading extracellular matrix proteins, and can act on several non-matrix proteins such as big endothelin-1 and beta-type CGRP, promoting vasoconstriction. It appears to have a role in myocardial cell death pathways and contributes to myocardial oxidative stress by regulating the activity of GSK3 beta. The C-terminal non-catalytic fragment of MMP-2 possesses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro. The pro-peptide is processed by MMP-14 (MT-MMP-1) and MMP-16 (MT-MMP-3). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrin/beta3. Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast, and prostate.
Swiss-Prot Accession Number: P08253
PublicationsInhibition of cytokine signaling by ruxolitinib and implactions for COVID-19 treatment (2020) Yeleswaram S, Smith P, Burn T, Covington M, Juvekar A, Li Y, Squier P, Langmuir P Clinical Immunology
Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: Machine learning on proteomics from the DETECT cohort (2020) Bauer Y, de Bernard S, Hickey P, Ballard K, Cruz J, Cornelisse P, Chadha-Boreham H, Distler O, Rosenberg D, Doelberg M, Roux S, Nayler O, Lawrie A European Respiratory Journal
Von Willebrand factor and ADAMTS13 activity in relation to risk of dementia: a population-based study (2018) Wolters F, Boender J, de Vries P, Sonneveld M, Koudstaal P, de Maat M, Franco O, Ikram M, Leebeek F, Ikram MA Scientific Reports 2018 Apr
Carbon nanotube and nanofiber exposure and sputum and blood biomarkers of early effect among U.S. workers (2018) Beard JD, Erdely A, Dahm MM, de Perio MA, Birch ME, Evans DE, Fernback JE, Eye T, Kodali V, Mercer RR, Bertke SJ, Schubauer-Berigan MK Environmental Internation 116 (2018)
Synergistic Cytokine Effects as Apremilast Response Predictors in Patients With Psoriasis (2018) Garcet S, Nograles K, Correa da Rosa J, Schafer PH, Krueger JG Journal of Allergy and Clinical Immunology
Early Plasma Matrix Metalloproteinase Profiles: A Novel Pathway in Pediatric Acute Respiratory Distress Syndrom (2018) Zinter MS, Delucchi KL, Kong MY, Orwoll BE, Spicer AS, Lim MJ, Alkhouli MF, Ratiu AE, McKenzie AV, McQuillen PS, Dvorak CC, Calfee CS, Matthay MA, Sapru A American Journal of Respiratory and Critical Care Medicine
Serum Apolipoprotein E and Other Inflammatory Markers Can Identify Non-Responding Patients to a Dendritic Cell Vaccine (2018) Leeman H, Kaminska E, Green D, Bodman-Smith M, Gravett A, Bodman-Smith K, Copier J, Coulton G, Fusi A, Dalgleish AG Translational Oncology
The role of anxious distress in immune dysregulation in patients with major depressive disorder. (2017) Gaspersz R, Lamers F, Wittenberg G, Beekman ATF, van Hemert AM, Schoevers RA, Penninx BWJH Transl Psychiatry
High false-positive rate of a putative biomarker test to aid in the diagnosis of schizophrenia (2016) Wehler CA, Preskorn, SH Journal of Clinical Psychiatry
Effects of Acute Endurance Exercise on Plasma Protein Profiles of Endurance-Trained and Untrained Individuals over Time (2016) Schild M, Eichner G, Beiter T, Zuegel M, Niess AM, Steinacker JM, Mooren FC Mediators of Inflammation
Altered Cerebrospinal Fluid Proteins in Smith–Lemli– (2016) Cologna SM, Shieh C, Toth CL, Cougnoux A, Burkert KR, Bianconi SE, Wassif CA, Porter FD American Journal of Medical Genetics Part A
Cytokine Production Capacity in Depression and Anxiety (2016) Vogelzangs N, De Jonge P, Smit JH, Bahn S, Penninx BW Translational Psychiatry
Biological stress systems, adverse life events and the improvement of chronic multi-site musculoskeletal pain across a 6-year follow-up. (2016) Generaal E, Vogelzangs N, Macfarlane GJ, Geenen R, Smit JH, de Geus EJ, Dekker J, Penninx BW. J Pain
Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study. (2015) Generaal E, Vogelzangs N, Macfarlane GJ, Geenen R, Smit JH, de Geus EJ, Penninx BW, Dekker J. Ann Rheum Dis. 2015 Apr 22. pii: annrheumdis-2014-206741. doi: 10.1136/annrheumdis-2014-206741. [Epub ahead of print]
Basal inflammation and innate immune response in chronic multisite musculoskeletal pain. (2014) Generaal E, Vogelzangs N, Macfarlane GJ, Geenen R, Smit JH, Dekker J, Penninx BW. Pain. 2014 Aug;155(8):1605-12. doi: 10.1016/j.pain.2014.05.007. Epub 2014 May 9.
Intracellular Aggregation of Multimodal Silica Nanoparticles for (2013) Jokerst JV, Khademi C, Gambhir SS Sci Transl Med. 2013 Mar 20;5(177):177ra35
Impact of Sunitinib on Human Thyroid Cancer Cells (2013) Grosse J, Warnke E, Pohl F, Magnusson NE, Wehland M, Infanger M, Eilles C, Grimm D Cell Physiol Biochem. 2013 Jul 12;32(1):154-170
Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively healthy older adults (2013) Mattsson N, Insel P, Nosheny R, Trojanowski JQ, Shaw LM, Jack Jr. CR, Tosun D, Weiner M, Alzheimer's Disease Neuroimaging Initiative Neurobiology of Aging, Available online 1 October 2013
Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space (2013) Ma X, Pietsch J, Wehland M, Schulz H, Saar K, Hübner N, Bauer J, Braun M, Schwarzwälder A, Segerer J, Birlem M, Horn A, Hemmersbach R, Waßer K, Grosse J, Infanger M, Grimm D FASEB J. 2013 Nov 6. [Epub ahead of print]
First-in-Human Phase I Study of PRS-050 (Angiocal), an Anticalin Targeting and Antagonizing VEGF-A, in Patients with Advanced Solid Tumors (2013) Mross K, Richly H, Fischer R, Scharr D, Büchert M, Stern A, Gille H, Audoly LP, Scheulen ME PLoS One. 2013 Dec 13;8(12):e83232
Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status (2012) Pellis L, van Erk MJ, van Ommen B, Bakker GCM, Hendriks HFJ, Cnubben NHP, Kleemann R, van Someren EP, Bobeldijk I, Rubingh CM, Wopereis S Metabolomics
Identification of blood-based molecular signatures for prediction of response and relapse in schizophrenia patients (2012) Schwarz E, Guest PC, Steiner J, Bogerts B, Bahn S Translational Psychiatry (2012) 2, e82
Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses (2012) Joubert MK, Hokom M, Eakin C, Zhou L, Deshpande M, Baker MP, Goletz TJ, Kerwin BA, Chirmule N, Narhi LO, Jawa V J Biol Chem. 2012 Jul 20;287(30):25266-79
Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma (2012) Xu BJ, An QA, Srinivasa Gowda S, Yan W, Pierce LA, Abel TW, Rush SZ, Cooper MK, Ye F, Shyr Y, Weaver KD, Thompson RC Int J Oncol. 2012 Jun;40(6):1995-2003
Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease (2012) Doecke JD, Laws SM, Faux NG, Wilson W, Burnham SC, Lam CP, Mondal A, Bedo J, Bush AI, Brown B, De Ruyck K, Ellis KA, Fowler C, Gupta VB, Head R, Macaulay SL, Pertile K, Rowe CC, Rembach A, Rodrigues M, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Ames D, Masters CL, Martins RN; for the Alzheimer's Disease Neuroimaging Initiative and Australian Imaging Biomarker and Lifestyle Research Group Arch Neurol. 2012 Jul 16:1-8
Biomarker analysis of Morquio syndrome: Identification of disease state and drug responsive markers (2011) Martell L, Lau K, Mei M, Burnett V, Decker C, Foehr ED Orphanet Journal of Rare Diseases 2011, 6:84
Treatment of experimental anterior and intermediate uveitis by a dexamethasone intravitreal implant (2011) Ghosn CR, Li Y, Orilla WC, Lin T, Wheeler L, Burke JA, Robinson MR, Whitcup SM Invest Ophthalmol Vis Sci. 2011 May 2;52(6):2917-23
Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase 1/2 study in patients with myelofibrosis (2011) Guglielmelli P, Barosi G, Rambaldi A, Marchioli R, Masciulli A, Tozzi L, Biamonte F, Bartalucci N, Gattoni E, Lupo ML, Finazzi G, Pancrazzi A, Antonioli E, Susini MC, Pieri L, Malevolti E, Usala E, Occhini U, Grossi A, Caglio S, Paratore S, Bosi A, Barbui T, Vannucchi AM Blood. 2011 Jul 1. [Epub ahead of print]
Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis (2010) Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A N Engl J Med. 363: 1117-27.
Validation of a Blood-Based Laboratory Test to Aid in the Confirmation of a Diagnosis of Schizophrenia (2010) Schwarz E, Izmailov R, Spain M, Barnes A, Mapes JP, Guest PC, Rahmoune H, Pietsch S, Leweke FM, Rothermundt M, Steiner J, Koethe D, Kranaster L, Ohrmann P, Suslow T, Levin Y, Bogerts B, (JM) van Beveren N, McAllister G, Weber N, Niebuhr D, Cowan D, Yolken RH, Bahn S Biomark Insights5: 39–47.
Classification of Alcohol Abuse by Plasma Protein Biomarkers. (2010) Freeman WM, Salzberg AC, Gonzales SW, Grant KA, Vrana KE Biol Psychiatry 68: 219-22.
Plasma biomarkers in carbon monoxide poisoning. (2010) Thom SR, Bhopale VM, Milovanova TM, Hardy KR, Logue CJ, Lambert DS, Troxel AB, Ballard K, Eisinger D Clin Toxicol (Phila) 48: 47-56.
Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma. (2008) Ding Y, Boguslawski EA, Berghuis BD, Young JJ, Zhang Z, Hardy K, Furge K, Kort E, Frankel AE, Hay RV, Resau JH, Duesbery NS Mol Cancer Ther 7: 648-658.
Biomarker analysis by fluorokine multianalyte profiling distinguishes patients requiring intervention from patients with long-term quiescent coronary artery disease: a potential approach to identify atherosclerotic disease progression. (2008) Gurbel PA, Kreutz RP, Bliden KP, DiChiara J, Tantry US Am Heart J 155: 56-61.
Phase I study of eptifibatide in patients with sickle cell anaemia. (2007) Lee SP, Ataga KI, Zayed M, Manganello JM, Orringer EP, Phillips DR, Parise LV Br J Haematol 139: 612-620.