Affinage

MMP2

72 kDa type IV collagenase · UniProt P08253

Length
660 aa
Mass
73.9 kDa
Annotated
2026-06-10
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MMP-2 (gelatinase A) is a zinc-dependent endopeptidase that remodels the extracellular matrix and, through proteolysis of structural and signaling proteins, governs cell invasion, fibrosis, vascular and cardiac homeostasis, and neuronal and adipocyte differentiation (PMID:19221481, PMID:25869489). It is secreted as a latent proenzyme whose activation occurs at the cell surface through a membrane-bound MT1-MMP (MMP-14) mechanism that requires collagen I or β1-integrin cues, generating active enzyme that associates with the tumor or fibroblast surface (PMID:10408832, PMID:22342364, PMID:12456388); this activation is controlled by TIMP-2, whose binding to proMMP-2 and inhibitory potency depend on extracellular c-Src phosphorylation at Y90 (PMID:30227959), while multi-site phosphorylation of MMP-2 itself, including by PKC, negatively regulates its catalytic activity (PMID:17435175). Once active, MMP-2 cleaves ECM substrates such as fibronectin, vitronectin, and collagen I into fragments that drive integrin-dependent adhesion and metastasis (PMID:19221481), and it processes non-ECM substrates including pro-NGF to mature NGF to control sympathetic nerve sprouting (PMID:20683769). MMP-2 transcription is induced by Src via the ERK/Sp1 axis (PMID:16453304), by PKA through Ets-2 and phospho-p53 in trophoblasts (PMID:19939245), and by HIF-2α under hypoxia (PMID:35802383), and is suppressed by the actin–MRTF-A/B contractile gene program (PMID:22449415). Beyond its canonical extracellular role, MMP-2 localizes intracellularly to the mitochondria-associated membrane where it cleaves calreticulin (PMID:24375642), to sarcomere Z-lines, nuclear membrane, and mitochondria of skeletal muscle (PMID:24905939), and to the platelet cytosol from which it translocates to the membrane upon collagen-stimulated aggregation (PMID:9843180). Genetically, MMP-2 acts upstream of TGF-β activation and noncanonical Erk1/2/Smad2 signaling in Marfan aortopathy (PMID:22550139), exerts a cardioprotective, anti-inflammatory role in cytokine-driven cardiomyopathy (PMID:15937097), and promotes adipogenesis (PMID:25869489) and Purkinje-cell dendritogenesis (PMID:24652381).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 Medium

    Established that MMP-2 and MT1-MMP are co-expressed at sites of tissue invasion alongside their collagen IV substrate, framing the membrane activation axis in a physiological invasion context.

    Evidence In situ hybridization and immunostaining of extravillous cytotrophoblasts in placental bed

    PMID:9294857

    Open questions at the time
    • Co-localization only, no functional perturbation
    • Did not demonstrate direct activation event
  2. 1998 Medium

    Showed MMP-2 has an intracellular pool that mobilizes upon stimulation, the first hint that its biology extends beyond constitutive secretion.

    Evidence Immunogold EM and flow cytometry of resting and collagen-aggregated platelets

    PMID:9843180

    Open questions at the time
    • Mechanism of cytosol-to-membrane translocation unknown
    • How cytosolic MMP-2 escapes the secretory pathway unresolved
  3. 1999 Medium

    Identified collagen I and β1 integrin as the specific signals triggering membrane-bound proMMP-2 activation on fibroblasts, defining the activation triggers.

    Evidence Carcinoma–fibroblast co-culture with collagen gel stimulation and anti-β1 integrin perturbation, zymography

    PMID:10408832

    Open questions at the time
    • Membrane metalloproteinase identity inferred, not directly proven here
    • Single lab cell-based reconstitution
  4. 2002 Medium

    Connected mechanical stretch to MMP-2 activation via MT1-MMP and EMMPRIN, linking biophysical cues to the activation machinery.

    Evidence Cyclic stretch of lung endothelial cells with MMP inhibitor, zymography and RT-PCR

    PMID:12456388

    Open questions at the time
    • MT1-MMP role inferred from pharmacological inhibition
    • EMMPRIN mechanistic link correlative
  5. 2006 High

    Mapped the transcriptional route from Src oncogene through ERK to the Sp1 site on the MMP-2 promoter, defining an inducible expression pathway.

    Evidence Promoter-reporter mutagenesis, EMSA, dominant-negative ERK-2 in cells

    PMID:16453304

    Open questions at the time
    • Did not address activation/secretion regulation
    • Single-cell-type promoter analysis
  6. 2007 High

    Revealed phosphorylation as a direct post-translational brake on MMP-2 catalysis, adding a layer of regulation beyond proenzyme activation.

    Evidence MS site mapping, in vitro PKC phosphorylation, alkaline phosphatase dephosphorylation, activity assays

    PMID:17435175

    Open questions at the time
    • In vivo kinase(s) for each site not identified
    • Phosphatase counter-regulators unknown
  7. 2009 High

    Demonstrated that active MMP-2 cleaves ECM proteins into pro-invasive fragments and is required in vivo for metastatic colonization, anchoring its catalytic role to disease outcome.

    Evidence 3D omentum culture, ECM cleavage assays, siRNA, blocking antibody, xenograft

    PMID:19221481

    Open questions at the time
    • Integrin receptors for cleaved fragments not individually defined
    • Relative contribution of each ECM substrate unresolved
  8. 2012 High

    Placed MMP-2 genetically upstream of TGF-β activation and noncanonical Erk1/2/Smad2 signaling in aortic disease, establishing a causal disease mechanism.

    Evidence MMP-2 KO crossed into Fbn1(mgR/mgR) Marfan mice, survival, zymography, pathway Western blots

    PMID:22550139

    Open questions at the time
    • Direct TGF-β latency substrate of MMP-2 not identified
    • Cell type responsible not pinpointed
  9. 2013 High

    Defined a precise intracellular niche for MMP-2 at the mitochondria-associated membrane with calreticulin as a candidate substrate, expanding its role into ER–mitochondrial Ca2+ biology.

    Evidence Immunogold EM, MMP-2:HaloTag imaging, subcellular fractionation, in vitro proteolysis of calreticulin

    PMID:24375642

    Open questions at the time
    • In vivo significance of calreticulin cleavage untested
    • How MMP-2 reaches the MAM cytoplasmic face unresolved
  10. 2018 High

    Showed extracellular c-Src phosphorylates TIMP-2 at Y90 to control its binding to proMMP-2 and inhibitory potency, identifying a phosphorylation switch on the inhibitor side of the activation complex.

    Evidence Extracellular kinase assay, Y90 non-phosphorylatable mutant, co-IP, inhibition assays

    PMID:30227959

    Open questions at the time
    • In vivo relevance of extracellular Src phosphorylation untested
    • Phosphatase reversing Y90 unknown
  11. 2022 Medium

    Identified HIF-2α (not HIF-1α) as the hypoxia-responsive transcriptional driver of MMP-2 in scleral fibroblasts and an MMP-2/eNOS interaction in vascular aging, diversifying its regulatory and substrate repertoire.

    Evidence HIF-2A siRNA and conditional knockout mice; MMP-2 siRNA, co-IP with eNOS, desmosine and cGMP measurement

    PMID:34586381 PMID:35802383

    Open questions at the time
    • MMP-2/eNOS interaction surface and functional consequence not structurally defined
    • Whether eNOS is a cleavage substrate or binding partner only unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MMP-2 partitions between extracellular and intracellular (MAM, sarcomere, platelet cytosol) pools, and how its non-ECM substrate set is selected in each compartment, remains unresolved.
  • No unifying model for intracellular targeting versus secretion
  • Compartment-specific substrate repertoire largely uncharacterized
  • Physiological in vivo substrates of intracellular MMP-2 not validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005576 extracellular region 3 GO:0005739 mitochondrion 3 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ITGAVITGB3MMP14NOS3SRCTIMP2
Complex memberships
MT1-MMP/TIMP-2/proMMP-2 activation complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 MMP-2 is phosphorylated on at least five sites (including threonine and serine residues) in mammalian cells, and phosphorylation by protein kinase C significantly modulates its enzymatic activity; dephosphorylation with alkaline phosphatase increases MMP-2 activity, establishing phosphorylation as a negative regulatory post-translational modification. Mass spectrometry (site identification), 2D immunoblot, in vitro PKC phosphorylation assay, gelatin dequenching assay, zymography, kinetic parameter measurement, alkaline phosphatase dephosphorylation FASEB journal High 17435175
2018 TIMP-2 is phosphorylated at Y90 by secreted c-Src tyrosine kinase in the extracellular space; this phosphorylation significantly enhances TIMP-2 potency as an MMP-2 inhibitor and is essential for TIMP-2 binding to latent proMMP-2, thereby controlling proMMP-2 activation. Extracellular kinase assay, site-directed mutagenesis (non-phosphorylatable Y90 mutant), co-immunoprecipitation, enzymatic inhibition assay iScience High 30227959
1998 In resting platelets, MMP-2 is distributed in the cytosol without association with granules; upon collagen-stimulated aggregation, MMP-2 translocates from the cytosol to the extracellular space and associates with the platelet plasma membrane, where it mediates the ADP- and thromboxane-independent component of aggregation. Immunogold electron microscopy, flow cytometry, Western blot, zymography Thrombosis and haemostasis Medium 9843180
2013 MMP-2 is principally localized to the mitochondria-associated membrane (MAM, a subdomain of the endoplasmic reticulum) in cardiac cells rather than to mitochondria proper; MAM-localized MMP-2 can proteolyze calreticulin in vitro, suggesting a role in ER–mitochondrial Ca2+ signaling. Immunogold electron microscopy (heart sections), immunofluorescence of MMP-2:HaloTag fusion protein, subcellular fractionation (purified mitochondria vs. MAM), in vitro proteolysis assay American journal of physiology. Heart and circulatory physiology High 24375642
2012 MMP-2 deletion in Marfan syndrome (Fbn1(mgR/mgR)) mice inhibited TGF-β activation and phosphorylation of Erk1/2 and Smad2, and prolonged lifespan, establishing that MMP-2 acts upstream of TGF-β activation and the noncanonical Erk1/2 signaling cascade in aortic dilatation. Genetic knockout (MMP-2-deficient Fbn1(mgR/mgR) mice), gelatin zymography, Western blot, life table analysis, aortic histology Circulation research High 22550139
2006 Src oncogene induces MMP-2 transcription via the ERK/Sp1 pathway; the Sp1 binding site at −91/−84 of the human MMP-2 promoter is the major responsive element, and ERK inhibition (PD98059) or dominant-negative ERK-2 blocks Src-induced MMP-2 promoter activity and Sp1 DNA binding. RT-PCR, promoter-reporter assay, deletion/mutation analysis, EMSA, dominant-negative ERK-2 expression, pharmacological inhibitors Journal of cellular physiology High 16453304
2002 Cyclic mechanical stretch of lung microvascular endothelial cells increases release and activation of MMP-2 through an MT1-MMP mechanism, preceded by upregulation of EMMPRIN; MT1-MMP inhibition (via a hydroxamic acid MMP inhibitor) blocks stretch-induced MMP-2 activation. Cyclic stretch Flexercell system, gelatin zymography, reverse zymography, Western blot, RT-PCR, pharmacological inhibition American journal of physiology. Lung cellular and molecular physiology Medium 12456388
1997 MT1-MMP and MMP-2 mRNAs are co-expressed and co-localized in extravillous cytotrophoblasts invading the placental bed, and both co-localize with their substrate type IV collagen, indicating that the MT1-MMP/MMP-2/collagen IV axis cooperates in trophoblast invasion. In situ hybridization, cytokeratin immunostaining on serial sections of normal and ectopic placentas Molecular human reproduction Medium 9294857
2009 MMP-2 is proteolytically activated upon ovarian cancer cell adhesion to the omentum and cleaves fibronectin, vitronectin, and collagen I into fragments that accelerate cancer cell adhesion and invasion via integrin receptors; in vivo siRNA or antibody blockade of MMP-2 before adhesion significantly reduced metastatic tumor number and weight. 3D organotypic omentum culture, zymography, ECM substrate cleavage assay, siRNA knockdown, blocking antibody, xenograft mouse model Cell cycle High 19221481
1999 In the ovarian tumor microenvironment, carcinoma cell–fibroblast contact stimulates proMMP-2 release from fibroblasts; collagen I (but not other ECM components) and β1 integrin antibody trigger activation of proMMP-2 by a membrane-bound metalloproteinase on tumor-derived fibroblasts, generating active MMP-2 that associates with tumor cell surfaces. Co-culture experiments, conditioned medium analysis, zymography, collagen gel stimulation, antibody perturbation (anti-β1 integrin) British journal of cancer Medium 10408832
2005 Selective MMP-2 gene knockout in TNF-α transgenic cardiomyopathy mice reduced survival and exacerbated cardiac dysfunction with increased myocardial macrophage infiltration and proinflammatory cytokines, demonstrating a cardioprotective role for MMP-2 in cytokine-induced cardiomyopathy. MMP-2 knockout crossed with TNF-α transgenic mice, survival analysis, echocardiography, zymography, immunohistochemistry, cytokine measurement American journal of physiology. Heart and circulatory physiology High 15937097
2007 Cardiac-specific transgenic overexpression of active MMP-2 abolishes ischemic preconditioning cardioprotection and causes mitochondrial ultrastructural abnormalities and impaired respiration, establishing MMP-2 as a negative regulator of mitochondrial function under oxidative stress. Cardiac-specific transgenic mouse (MMP-2 Tg), ex vivo ischemia–reperfusion model, electron microscopy (mitochondrial ultrastructure), mitochondrial respiration assay, infarct size measurement Biochemical and biophysical research communications Medium 17475219
2011 HMGA1 directly binds the MMP-2 promoter in vivo in large-cell lung cancer cells (chromatin immunoprecipitation), upregulates MMP-2 mRNA and protein expression, and MMP-2 knockdown blocks HMGA1-induced anchorage-independent growth and invasion. ChIP, RT-PCR, siRNA knockdown, anchorage-independent growth assay, invasion assay Molecular cancer research Medium 19903768
2012 MMP-14 (MT1-MMP) knockdown inhibits proMMP-2 activation in Dupuytren's disease fibroblasts, and knockdown of MMP-2 (but not MMP-1, -3, or -13) inhibits fibroblast-mediated collagen contraction, establishing MMP-14 as the key activator of proMMP-2 and MMP-2 as essential for cell-mediated contraction in this fibrotic condition. siRNA knockdown, fibroblast-populated collagen lattice (FPCL) contraction assay, zymography, gene expression profiling Biochimica et biophysica acta Medium 22342364
2008 In human intervertebral disc degeneration, active MMP-2 levels correlate significantly with MMP-14 expression (but less strongly with TIMP-2), indicating that MMP-14 activates proMMP-2 during disc degeneration via the MT1-MMP/TIMP-2 activation complex. Gelatin zymography (MMP-2 quantification), immunohistochemistry (MMP-14, TIMP-2), correlation analysis across 56 graded human IVDs The Journal of pathology Low 18200629
2002 Adenosine A1 receptor agonist (CHA) stimulates MMP-2 secretion from trabecular meshwork cells via ERK1/2 activation; this response is blocked by an A1 receptor antagonist (CPT) and the ERK pathway inhibitor U0126, placing ERK1/2 downstream of A1 receptor activation and upstream of MMP-2 secretion. Cell culture, CHA/CPT/U0126 pharmacological experiments, ELISA (MMP-2 secretion), Western blot (ERK phosphorylation), dose-response analysis Investigative ophthalmology & visual science Medium 12202524
2009 Ets-2 and phospho-p53 mediate PKA (cAMP/Forskolin)-induced MMP-2 expression and trophoblast invasiveness; antisense inhibition of Ets-2 and p53 reduces MMP-2 mRNA, secretion, and transwell invasion. Northern blot, RT-PCR, EMSA, Western blot, antisense transfection, zymography, transwell invasion assay Reproductive biology and endocrinology Medium 19939245
2015 Intracellular MMP-2 is concentrated at sarcomere Z-lines, the nuclear membrane, and mitochondria of skeletal muscle fibers, with gelatinolytic activity predominantly in fast-twitch type II fibers; activity is reduced by metalloprotease inhibitors (EDTA, CTT2) but not a cysteine protease inhibitor, and decreases with high-intensity interval training. Immunohistochemistry, immunogold electron microscopy, in situ zymography, pharmacological inhibitors Journal of cellular physiology Medium 24905939
2010 MMP-2 inhibition in medulloblastoma tumor cells reduces SDF-1 in tumor-conditioned medium, impairs SDF-1/CXCR4 signaling, and decreases tropism of human umbilical cord blood-derived stem cells toward tumors both in vitro and in vivo. Adenoviral siRNA (Ad-MMP-2 si), transwell migration assay, Western blot, immunohistochemistry, in vivo tumor model Gene therapy Medium 21368903
2022 MMP-2 knockdown in aging mice attenuates age-dependent carotid stiffness by decreasing elastin degradation (lower plasma desmosine) and increasing eNOS phosphorylation and vascular cGMP; an age-dependent direct protein–protein interaction between MMP-2 and eNOS was observed, suggesting MMP-2 inhibits eNOS bioavailability. siRNA knockdown (tail-vein injection), pulse wave velocity, Western blot, co-immunoprecipitation (MMP-2/eNOS interaction), plasma desmosine ELISA, cGMP measurement, human cohort correlation Cardiovascular research Medium 34586381
2010 MMP-2 is expressed and secreted by sympathetic neurons and, together with MT1-MMP, converts pro-NGF to mature NGF; pharmacological MMP-2 inhibition increases pro-NGF accumulation and reduces HFES-induced neurite outgrowth, establishing MMP-2 as a pro-NGF convertase controlling sympathetic nerve sprouting. Cell culture of superior cervical ganglia neurons, high-frequency electrical field stimulation, RT-PCR, Western blot, zymography, pharmacological MMP-2 inhibition, neurite outgrowth measurement Cellular and molecular neurobiology Medium 20683769
2011 WISP-1 increases MMP-2 expression and chondrosarcoma cell migration via α5β1 integrin → FAK → MEK/ERK → NF-κB/p65 pathway; blocking α5β1, MEK (PD98059/U0126), or NF-κB inhibits WISP-1-induced MMP-2 upregulation and migration. Pharmacological inhibitors, blocking antibody (α5β1), phosphorylation Western blot, NF-κB luciferase reporter, ChIP (p65 on MMP-2 promoter), migration assay Biochemical pharmacology Medium 21453685
2003 Zebrafish MMP-2 (>80% identity to human MMP-2) is expressed from the one-cell stage (maternal origin); morpholino antisense knockdown causes a truncated embryonic axis beginning at 12 h, demonstrating an essential role for MMP-2 in early vertebrate embryogenesis—in contrast to mouse knockout studies. In situ hybridization, RT-PCR, gelatin zymography, antisense morpholino oligonucleotide injection, developmental axis marker analysis Development genes and evolution Medium 12898250
2014 MMP-2 deficiency in Purkinje cells of MMP-2−/− mice leads to reduced soma growth, smaller dendritic trees, decreased arborization, and increased spine density with reduced spine length; proteomics identified elevated phospho-CRMP1 in MMP-2−/− cerebella as a potential mediator of aberrant dendritogenesis. 2D-DIGE proteomics, Western blot, immunohistochemistry, morphometric analysis, MMP-2 knockout mice Brain structure & function Medium 24652381
2003 Estrogen (E2) at 10−10 M increases MMP-2 activity (~2.2-fold) and protein expression (~2.5-fold) in retinal pigment epithelium cells; this effect is abolished by the NF-κB inhibitor PDTC, placing NF-κB downstream of estrogen receptor activation and upstream of MMP-2 regulation. Zymography, Western blot, PDTC inhibition, estrogen receptor transfection reporter assay Investigative ophthalmology & visual science Medium 12506055
2011 In rheumatoid arthritis synovial fibroblasts, recombinant MMP-2 inactivates NF-κB and suppresses cartilage degradation, whereas endogenous MMP-2 suppression (siRNA) activates NF-κB and increases TNF-α and IL-17 secretion, revealing an anti-inflammatory function of MMP-2 distinct from the pro-inflammatory role of MMP-9. siRNA knockdown, recombinant protein treatment, specific inhibitors, NF-κB activation Western blot, ELISA for cytokines, cartilage degradation assay (1,9-DMMB), invasion and migration assays Rheumatology (Oxford) Medium 24982240
2022 HIF-2α (not HIF-1α) mediates hypoxia-induced MMP-2 upregulation in scleral fibroblasts; HIF-2A siRNA silencing abolishes hypoxia-induced MMP-2 expression and FD-induced collagen degradation and myopia development in mice, whereas HIF-1α knockdown does not affect MMP-2 upregulation. HIF-2A siRNA in human scleral fibroblasts (1% O2), AAV8-Cre scleral injection in HIF-2αfl/fl and HIF-1αfl/fl mice, Western blot, qRT-PCR, pulse refraction measurement Investigative ophthalmology & visual science Medium 35802383
2016 In iPSC-derived cortical neurons with MAPT mutations, elevated MMP-2 (and MMP-9) levels contribute to stress-induced neuronal death; MMP-2/9 inhibitors protect patient neurons, and recombinant MMP-2 decreases neuronal survival, demonstrating a direct cytotoxic function of secreted MMP-2 toward neurons. iPSC-derived cortical neurons, MMP inhibitor treatment, recombinant MMP-2/9 treatment, ERK pathway inhibitor, cell viability assay Stem cell reports Medium 27594586
2015 MMP-2 promotes murine adipogenesis: MMP-2-deficient MEFs show 90% reduced lipid accumulation and reduced pro-adipogenic marker expression; MMP-2 shRNA knockdown in 3T3-F442A preadipocytes impairs differentiation while MMP-2 overexpression markedly enhances it. Mmp2 KO MEF differentiation, shRNA knockdown, Mmp2 overexpression, oil-red-O staining, marker gene expression, in vivo fat pad model Biochimica et biophysica acta Medium 25869489
2011 MMP-2 siRNA knockdown in glioma cells blocks radiation-enhanced invasion by inhibiting VEGF, VEGFR-2, pVEGFR-2, p-FAK, and p-p38 signaling and induces apoptosis; in vivo MMP-2 siRNA significantly reduces intracranial tumor growth. Plasmid-mediated siRNA, Western blot, invasion/migration assays, TUNEL staining, intracranial xenograft model PloS one Medium 21698233
2014 S100A8/A9 expression selectively down-regulates MMP-2 expression and activity in carcinoma cells; conversely, silencing S100A8/A9 increases MMP-2 activity and invasion; MMP-2 silencing reduces the malignant phenotype, and 3D collagen growth increases MMP-2 expression relative to 2D. Transfection of S100A8/A9 expression constructs, siRNA knockdown of S100A8/A9 and MMP-2, zymography, invasion/migration assays, 3D collagen substrate The international journal of biochemistry & cell biology Medium 25236491
2012 In fibroblasts, myofibroblast contractility (driven by F-actin assembly, serum, or TGF-β) suppresses MMP-2 expression inversely to smooth muscle α-actin expression; MRTF-A/B knockdown (myocardin-like factors that drive contractile gene expression) relieves serum/TGF-β-induced MMP-2 suppression, linking the actin–MRTF–contractile gene axis to MMP-2 regulation. 3D collagen lattice under tension vs. stress release, 2D culture with pharmacological F-actin modulators, RNAi knockdown of MRTF-A/B, Western blot Experimental cell research Medium 22449415
2012 BMP2 induces MMP-2 secretion and activation in pancreatic PANC-1 cells via ROS accumulation and ERK phosphorylation; ROS scavenger 2-MPG or ERK inhibitor PD98059 reduces BMP2-induced MMP-2 activation and cell invasion. BMP2 stimulation, ROS scavenger and ERK inhibitor treatment, zymography, Western blot, invasion assay Frontiers in bioscience Low 22652796
2003 MMP-2 is expressed as an active form on the membrane of human cervical cancer cells in a complex involving αvβ3 integrin and MT1-MMP, consistent with the αvβ3/MT1-MMP/TIMP-2 trimolecular activation complex mediating MMP-2 activation at the tumor cell surface. Subcellular membrane fractionation, Western blot, immunoprecipitation (MMP-2 with αvβ3 integrin), MT1-MMP expression analysis Journal of environmental pathology, toxicology and oncology Low 14533872

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography. Methods in molecular biology (Clifton, N.J.) 223 22674130
1996 MMP-2: expression, activation and inhibition. Enzyme & protein 186 8796994
2003 MMP-2 and MMP-9 synergize in promoting choroidal neovascularization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 156 14563686
2014 Endogenous MMP-9 and not MMP-2 promotes rheumatoid synovial fibroblast survival, inflammation and cartilage degradation. Rheumatology (Oxford, England) 154 24982240
2008 Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture. Clinical orthopaedics and related research 138 18425559
2009 MMP-2 functions as an early response protein in ovarian cancer metastasis. Cell cycle (Georgetown, Tex.) 125 19221481
2007 Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 123 17435175
2017 MMP-2 and 9 in Chronic Kidney Disease. International journal of molecular sciences 116 28397744
2003 Regulation of estrogen receptors and MMP-2 expression by estrogens in human retinal pigment epithelium. Investigative ophthalmology & visual science 112 12506055
2012 MMP-2 regulates Erk1/2 phosphorylation and aortic dilatation in Marfan syndrome. Circulation research 99 22550139
2011 MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells. PloS one 91 21698233
1998 Localization and translocation of MMP-2 during aggregation of human platelets. Thrombosis and haemostasis 91 9843180
2009 Overexpression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 85 19191857
2024 The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease. International journal of molecular sciences 82 39769454
2021 Inhibitors of gelatinases (MMP-2 and MMP-9) for the management of hematological malignancies. European journal of medicinal chemistry 80 34157437
2001 Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats. Biology of reproduction 79 11133670
2008 Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels. The Journal of pathology 73 18200629
2002 Adenosine A1 receptor modulation of MMP-2 secretion by trabecular meshwork cells. Investigative ophthalmology & visual science 72 12202524
2002 Mechanical stretch induces MMP-2 release and activation in lung endothelium: role of EMMPRIN. American journal of physiology. Lung cellular and molecular physiology 72 12456388
2015 MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2. PloS one 71 25803859
2006 Src oncogene activates MMP-2 expression via the ERK/Sp1 pathway. Journal of cellular physiology 69 16453304
2009 Upregulation of MMP-2 by HMGA1 promotes transformation in undifferentiated, large-cell lung cancer. Molecular cancer research : MCR 68 19903768
2006 The role of MMP-2 and MMP-9 polymorphisms in sporadic intracranial aneurysms. Journal of neurosurgery 66 16961137
2017 Heart failure and role of circulating MMP-2 and MMP-9. Panminerva medica 62 28399617
2005 Gelatinases (MMP-2 and MMP-9) are preferentially expressed by Th1 vs. Th2 cells. Journal of neuroimmunology 61 15885317
2019 The role of MMP-2 and MMP-9 in the metastasis and development of hypopharyngeal carcinoma. Brazilian journal of otorhinolaryngology 60 31882379
2011 WISP-1 increases MMP-2 expression and cell motility in human chondrosarcoma cells. Biochemical pharmacology 59 21453685
2014 Urinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignancies. British journal of cancer 58 25137018
2011 PERIOSTIN regulates MMP-2 expression via the αvβ3 integrin/ERK pathway in human periodontal ligament cells. Archives of oral biology 58 21885032
2007 Transgenic MMP-2 expression induces latent cardiac mitochondrial dysfunction. Biochemical and biophysical research communications 58 17475219
2005 Regulation of TIMP-2, MT1-MMP, and MMP-2 expression during C2C12 differentiation. Muscle & nerve 56 16003733
1999 Matrix metalloproteinases MMP-2, MMP-7 and MMP-9 in denervated human muscle. Neuroreport 56 10511442
2004 Alendronate regulates cell invasion and MMP-2 secretion in human osteosarcoma cell lines. Pediatric blood & cancer 55 15049011
2003 The expression of gelatinase A (MMP-2) is required for normal development of zebrafish embryos. Development genes and evolution 55 12898250
2000 MMP-2 expression during early avian cardiac and neural crest morphogenesis. The Anatomical record 55 10820319
1999 Predominance of MMP-1 and MMP-2 in epiretinal and subretinal membranes of proliferative vitreoretinopathy. Experimental eye research 55 9986746
2022 Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu. International journal of molecular sciences 53 36076910
2001 Role of MMP-2 in alveolar epithelial cell repair after bleomycin administration in rabbits. Laboratory investigation; a journal of technical methods and pathology 52 11555678
2016 Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms. The Journal of nutritional biochemistry 51 27260467
1999 MMP-2 release and activation in ovarian carcinoma: the role of fibroblasts. British journal of cancer 51 10408832
2017 Is dual inhibition of metalloenzymes HDAC-8 and MMP-2 a potential pharmacological target to combat hematological malignancies? Pharmacological research 50 28501516
2006 MMP-2 but not MMP-9 associated with COX-2 and survival in gastric cancer. Journal of clinical pathology 50 16731602
2018 MMP-2: is too low as bad as too high in the cardiovascular system? American journal of physiology. Heart and circulatory physiology 49 30118342
2005 MMP-2 expression in uveal melanoma: differential activation status dictated by the cellular environment. Molecular vision 48 16379022
1994 Collagen induced MMP-2 activation in human breast cancer. Breast cancer research and treatment 46 7881112
2022 Hypoxia-Induced Scleral HIF-2α Upregulation Contributes to Rises in MMP-2 Expression and Myopia Development in Mice. Investigative ophthalmology & visual science 44 35802383
2014 Pterostilbene suppresses oral cancer cell invasion by inhibiting MMP-2 expression. Expert opinion on therapeutic targets 44 25109417
2020 Targeted MMP-2 responsive chimeric polymersomes for therapy against colorectal cancer. Colloids and surfaces. B, Biointerfaces 43 32447200
2013 MMP-2 is localized to the mitochondria-associated membrane of the heart. American journal of physiology. Heart and circulatory physiology 42 24375642
2019 LOX inhibition downregulates MMP-2 and MMP-9 in gastric cancer tissues and cells. Journal of Cancer 41 31777578
2011 Differential expression of MMP-2, MMP-9 and PCNA in endometriosis and endometrial carcinoma. European journal of obstetrics, gynecology, and reproductive biology 41 22056701
2017 CXCL10 accelerates EMT and metastasis by MMP-2 in hepatocellular carcinoma. American journal of translational research 38 28670372
2012 MMP-14 and MMP-2 are key metalloproteases in Dupuytren's disease fibroblast-mediated contraction. Biochimica et biophysica acta 38 22342364
2008 Single-nucleotide polymorphisms of MMP-2 gene in stroke subtypes. Cerebrovascular diseases (Basel, Switzerland) 38 18560213
2005 Selective disruption of MMP-2 gene exacerbates myocardial inflammation and dysfunction in mice with cytokine-induced cardiomyopathy. American journal of physiology. Heart and circulatory physiology 38 15937097
2018 MMP-2 expression and correlation with pathology and MRI of glioma. Oncology letters 36 30675244
2015 Gelatinase A (MMP-2) promotes murine adipogenesis. Biochimica et biophysica acta 36 25869489
2010 Divergent role for MMP-2 in myelin breakdown and oligodendrocyte death following transient global ischemia. Journal of neuroscience research 36 19830840
1997 Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation. Molecular human reproduction 36 9294857
2018 Extracellular Phosphorylation of TIMP-2 by Secreted c-Src Tyrosine Kinase Controls MMP-2 Activity. iScience 35 30227959
2011 MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors. Gene therapy 35 21368903
2014 S100A8/A9 regulates MMP-2 expression and invasion and migration by carcinoma cells. The international journal of biochemistry & cell biology 34 25236491
2004 Dilating the degradome: matrix metalloproteinase 2 (MMP-2) cuts to the heart of the matter. The Biochemical journal 34 15508185
2009 Rosuvastatin inhibits MMP-2 expression and limits the progression of atherosclerosis in LDLR-deficient mice. Archives of medical research 33 19766896
2012 MMP-2 expression by fibroblasts is suppressed by the myofibroblast phenotype. Experimental cell research 32 22449415
2011 The distinct roles of MMP-2 and MMP-9 in acute DSS colitis. European journal of microbiology & immunology 32 24516737
2025 Matrix Metalloproteinase-2 (MMP-2): As an Essential Factor in Cancer Progression. Recent patents on anti-cancer drug discovery 31 37861020
2017 Blockade of MMP-2 and MMP-9 inhibits corneal lymphangiogenesis. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 31 28669039
2017 PKCζ, MMP‑2 and MMP‑9 expression in lung adenocarcinoma and association with a metastatic phenotype. Molecular medicine reports 31 28983601
2024 MMP-2 Responsive Peptide Hydrogel-Based Nanoplatform for Multimodal Tumor Therapy. International journal of nanomedicine 30 38187906
2006 Lymph node micrometastasis and its correlation with MMP-2 expression in gastric carcinoma. World journal of gastroenterology 30 16718824
2015 Immunohistochemical analysis on MMP-2 and MMP-9 for wound age determination. International journal of legal medicine 29 25753382
2014 Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2. Molecular and cellular biochemistry 29 25047892
2018 Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis. Experimental and therapeutic medicine 28 30186424
2016 MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations. Stem cell reports 28 27594586
2015 Intracellular MMP-2 activity in skeletal muscle is associated with type II fibers. Journal of cellular physiology 28 24905939
2012 Expression of MMP-2, TIMP-2, TGF-β1, and decorin in Dupuytren's contracture. Connective tissue research 27 22512703
2022 MMP-2 knockdown blunts age-dependent carotid stiffness by decreasing elastin degradation and augmenting eNOS activation. Cardiovascular research 26 34586381
2016 Modulation of Systemic Metabolism by MMP-2: From MMP-2 Deficiency in Mice to MMP-2 Deficiency in Patients. Comprehensive Physiology 26 27783864
2011 MMP(-2) expression in skeletal muscle after strength training. International journal of sports medicine 26 22095325
1998 Different expression patterns of MMP-2 and MMP-9 in breast cancer. Oncology reports 26 9625836
2022 Association of MMP-2 and MMP-9 Polymorphisms with Diabetes and Pathogenesis of Diabetic Complications. International journal of molecular sciences 25 36142480
2019 Epigallocatechin-3-gallate inhibits migration of human nasopharyngeal carcinoma cells by repressing MMP-2 expression. Journal of cellular physiology 25 31012106
2018 Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis. International journal of molecular sciences 25 29462885
2018 Eupatilin inhibits angiogenesis-mediated human hepatocellular metastasis by reducing MMP-2 and VEGF signaling. Bioorganic & medicinal chemistry letters 25 30177376
2016 Expression of metalloproteinases (MMP-2 and MMP-9) in basal-cell carcinoma. Molecular biology reports 25 27406386
2015 Association between MMP-2 expression and prostate cancer: A meta-analysis. Biomedical reports 25 26893846
2014 Heterogeneity of serum gelatinases MMP-2 and MMP-9 isoforms and charge variants. Journal of cellular and molecular medicine 25 24616914
2004 Fibronectin-induced COX-2 mediates MMP-2 expression and invasiveness of rhabdomyosarcoma. Biochemical and biophysical research communications 25 15120641
2014 MMP-2 mediates Purkinje cell morphogenesis and spine development in the mouse cerebellum. Brain structure & function 24 24652381
2013 Correlation between MMP-2 and NF-κ B expression of intracranial aneurysm. Asian Pacific journal of tropical medicine 24 23768831
2003 Membrane-associated MMP-2 in human cervical cancer. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 24 14533872
2016 May High MMP-2 and TIMP-2 Expressions Increase or Decrease the Aggressivity of Oral Cancer? Pathology oncology research : POR 23 27853937
2009 Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion. Reproductive biology and endocrinology : RB&E 23 19939245
2008 Clinicopathologic evaluation of immunohistochemical CD147 and MMP-2 expression in differentiated thyroid carcinoma. Japanese journal of clinical oncology 23 18664479
2019 Polymorphisms in gene MMP-2 modify the association of cadmium exposure with hypertension risk. Environment international 22 30684802
2018 miR-29b enhances prostate cancer cell invasion independently of MMP-2 expression. Cancer cell international 22 29440967
2012 BMP2 induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK. Frontiers in bioscience (Landmark edition) 22 22652796
2010 Sympathetic neurons express and secrete MMP-2 and MT1-MMP to control nerve sprouting via pro-NGF conversion. Cellular and molecular neurobiology 22 20683769
2016 Inhibition of MMP-2 and MMP-9 Activities by Limonium tetragonum Extract. Preventive nutrition and food science 21 27069904

Missed literature

Know a paper Affinage missed for MMP2? Flag it for the maintainers and the community.

No submissions yet.