Affinage

MMP9

Matrix metalloproteinase-9 · UniProt P14780

Round 2 corrected
Length
707 aa
Mass
78.5 kDa
Annotated
2026-04-28
130 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MMP9 (gelatinase B) is a secreted zinc-dependent endopeptidase that functions as a central regulator of extracellular matrix remodeling, angiogenesis, and immune cell mobilization. Secreted as a 92-kDa glycosylated proenzyme, it is activated by MMP-3-mediated stepwise propeptide cleavage, by HOCl/myeloperoxidase-generated oxidants acting on the cysteine switch, and by ADAM15, while its activity is constrained by TIMP-1 complexation, RECK, and thrombospondin-1 (PMID:1371271, PMID:36009335, PMID:9789069, PMID:11606713). MMP9 degrades collagens (types I, III, IV, V), gelatin, and non-ECM substrates including latent TGF-β (via CD44-mediated cell-surface docking), IL-8 (potentiating neutrophil chemotaxis ~10-fold), Kit-ligand (enabling hematopoietic stem cell mobilization from bone marrow niches), Syndecan-4, PAR1, and proBDNF, thereby linking proteolysis to angiogenesis, stem cell trafficking, inflammation, and synaptic plasticity (PMID:10652271, PMID:11023497, PMID:12062105, PMID:33246160, PMID:34330919). Transcription is driven by cooperative AP-1, NF-κB, and Sp-1 promoter elements in response to TNF-α, TPA, tPA-LRP signaling, and TLR2/p38 signaling, with PPARγ serving as a negative regulator through NF-κB inhibition (PMID:8426746, PMID:12960961, PMID:33636289).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1989 High

    Identification of MMP9 as a distinct 92-kDa secreted metalloproteinase with a five-domain architecture and type IV/V collagenase activity established it as a new MMP family member with unique structural features including a collagen V-homologous proline-rich domain.

    Evidence Protein purification, NH2-terminal sequencing, substrate digestion assays from SV40-transformed fibroblasts, macrophages, and fibrosarcoma cells

    PMID:2551898

    Open questions at the time
    • Crystal structure of full-length proMMP-9 not yet resolved
    • Physiological activators in vivo unknown
  2. 1992 High

    Demonstration that MMP-3 activates proMMP-9 through sequential propeptide cleavage at specific bonds (Glu40-Met41, Arg87-Phe88) established the paradigm of inter-MMP zymogen activation cascades, while TIMP-1 was shown to block intermediate-to-active conversion.

    Evidence In vitro reconstitution with purified enzymes, NH2-terminal sequencing of cleavage products, substrate digestion with multiple protease panels

    PMID:1371271 PMID:1400481

    Open questions at the time
    • Relative contributions of different activators in specific tissue contexts unknown
    • Structural basis of TIMP-1 inhibition of the intermediate not resolved
  3. 1993 High

    Mapping the transcriptional control of MMP9 to synergistic AP-1, NF-κB, and Sp-1 promoter elements explained how inflammatory cytokines (TNF-α) and phorbol esters (TPA) drive MMP9 induction, establishing the transcriptional framework for MMP9 regulation.

    Evidence Promoter deletion/mutation luciferase reporters, EMSA nuclear factor binding assays in osteosarcoma cells

    PMID:8426746

    Open questions at the time
    • Chromatin-level regulation (histone modifications, DNA methylation) not yet examined
    • Cell-type-specific enhancer usage not defined
  4. 1998 High

    MMP9-null mice revealed that MMP9 is required for growth plate vascularization, hypertrophic chondrocyte apoptosis, and ossification, and bone marrow transplantation rescue proved that bone-marrow-derived cells are the critical MMP9 source, establishing MMP9 as an angiogenic switch in skeletal development.

    Evidence Gene knockout mice, bone marrow transplantation rescue, organ culture angiogenesis assays

    PMID:9590175

    Open questions at the time
    • Direct angiogenic substrate released by MMP9 in growth plate not molecularly identified
    • Redundancy with other MMPs in ossification not fully tested
  5. 2000 High

    Three discoveries converged to define MMP9's non-ECM substrate repertoire and cell-surface regulation: CD44 was identified as a docking receptor localizing active MMP9 to the cell surface for TGF-β activation; inflammatory cell-derived MMP9 was shown to drive multistage skin carcinogenesis; and MMP9 was found to process IL-8 into a 10–27-fold more potent neutrophil chemotactic form.

    Evidence Co-immunoprecipitation and TGF-β cleavage assays; bone marrow chimera experiments in HPV16 transgenic mice; in vitro IL-8 cleavage with Ca²⁺ flux and chemotaxis readouts

    PMID:10652271 PMID:11023497 PMID:11081634

    Open questions at the time
    • Full repertoire of non-ECM substrates not systematically catalogued
    • Structural basis of CD44–MMP9 PEX domain interaction not resolved at atomic level
  6. 2001 High

    Discovery that NGAL stabilizes MMP9 against degradation (preserving enzymatic activity) and that thrombospondin-1 suppresses proMMP-9 activation in vivo revealed two opposing extracellular regulators that tune MMP9 bioavailability beyond TIMP-based inhibition.

    Evidence In vitro reconstitution of NGAL–MMP9 complex; TSP1-knockout/overexpression mice with in vitro activation suppression assays

    PMID:11486009 PMID:11606713

    Open questions at the time
    • Stoichiometry and structural basis of NGAL–MMP9 complex not fully defined
    • Whether TSP1 directly binds proMMP9 or acts indirectly not conclusively resolved
  7. 2002 High

    MMP9 was placed at the center of hematopoietic stem cell mobilization: SDF-1-induced MMP9 releases soluble Kit-ligand from the bone marrow niche, enabling c-Kit+ stem cell transfer to proliferative niches, as demonstrated by impaired sKitL release and HSC motility in MMP9−/− mice rescued by exogenous sKitL.

    Evidence MMP9 knockout mice, BM ablation, exogenous sKitL rescue, stem cell mobilization assays

    PMID:12062105

    Open questions at the time
    • Whether MMP9 cleaves Kit-ligand directly or via intermediate protease not fully resolved
    • Contribution of other MMPs to sKitL shedding not excluded
  8. 2002 High

    Parallel discoveries showed MMP9 contributes to aortic aneurysm formation (cooperatively with MMP-2 from distinct cell sources) and is released on membrane vesicles by endothelial cells during angiogenesis, while MMP9 induction in premetastatic lungs via VEGFR-1 signaling promotes metastatic colonization.

    Evidence Double-KO mice with macrophage reinfusion for AAA; vesicle ultrastructure/zymography/invasion assays; VEGFR-1 TK and MMP9 deletion metastasis models

    PMID:11839588 PMID:12208863 PMID:12398893

    Open questions at the time
    • Specific ECM substrates degraded by vesicle-associated MMP9 not identified
    • Whether vesicle-mediated MMP9 delivery is regulated independently of soluble secretion unknown
  9. 2003 High

    tPA was shown to upregulate MMP9 expression in brain endothelium via LRP signaling, linking the fibrinolytic system to MMP9-mediated blood-brain barrier degradation during stroke.

    Evidence RNAi knockdown of LRP, tPA-knockout mice, focal cerebral ischemia model

    PMID:12960961

    Open questions at the time
    • Downstream signaling cascade from LRP to MMP9 transcription not fully delineated
    • Whether LRP-MMP9 axis is relevant in non-stroke neurological injury unknown
  10. 2007 High

    The discovery that neutrophils uniquely release TIMP-free proMMP-9—which upon activation is an exceptionally potent proangiogenic stimulus at subnanomolar concentrations—explained why neutrophil-derived MMP9 has disproportionate biological impact compared to MMP9 from other sources.

    Evidence Granule purification, stoichiometric TIMP-1 complexation, in vivo chick CAM angiogenesis assay

    PMID:18077379

    Open questions at the time
    • Mechanism by which neutrophils package MMP9 without TIMP not determined
    • Whether TIMP-free status is regulated under different inflammatory conditions unclear
  11. 2015 High

    Endothelin-1/superoxide/MMP9 epistasis experiments established MMP9 as an effector of oxidative-stress-driven cardiac remodeling: superoxide upregulates MMP9, and genetic ablation of MMP9 rescues dilated cardiomyopathy independently of superoxide levels.

    Evidence Endothelin-1 hypomorphic mice, SOD mimetic rescue, MMP9 knockout, cardiac functional measurements

    PMID:25848038

    Open questions at the time
    • Specific cardiac ECM substrates degraded by MMP9 in this context not identified
    • Whether MMP9 catalytic activity or non-catalytic PEX signaling mediates the phenotype unclear
  12. 2020 Medium

    MMP9's substrate repertoire was extended to include PAR1 on pancreatic cancer cells (promoting mesenchymal transition) and Syndecan-4 in osteoarthritic cartilage (desensitizing chondrocytes to IL-1β signaling), demonstrating context-specific signaling consequences of MMP9-mediated ectodomain shedding.

    Evidence PAR1 cleavage assays with MMP9/PAR1 inhibitors; Sdc4 siRNA/inhibitor knockdown with pERK readout in chondrocytes

    PMID:32809114 PMID:33246160

    Open questions at the time
    • Structural determinants of MMP9 selectivity for PAR1 vs other PARs not defined
    • In vivo validation of Sdc4 shedding by MMP9 in animal OA models lacking
  13. 2021 Medium

    MMP9 was linked to stress-induced synaptic plasticity: glucocorticoid-driven secretory autophagy via FKBP51 releases MMP9, which cleaves proBDNF to mature BDNF in vivo, connecting neuroendocrine stress signaling to MMP9-dependent neurotrophin processing.

    Evidence Cellular secretory autophagy assays, in vivo brain microdialysis, FKBP51 manipulation, proBDNF/mBDNF cleavage measurement

    PMID:34330919

    Open questions at the time
    • Whether MMP9 cleaves proBDNF directly or via plasmin cascade not fully distinguished
    • Relevance to chronic stress and psychiatric phenotypes not established in knockout models
  14. 2022 High

    Biochemical reconstitution of the HOCl/myeloperoxidase-mediated cysteine switch oxidation mechanism showed concentration-dependent bidirectional regulation: low-concentration oxidants activate proMMP9, while high concentrations inactivate the enzyme, providing a rheostat for inflammatory MMP9 control.

    Evidence Fluorescence activity assays, gel zymography, MPO enzymatic system, competitive methionine inhibition

    PMID:36009335

    Open questions at the time
    • In vivo concentrations of HOCl at inflammatory sites relative to activation/inactivation thresholds not measured
    • Whether other MMPs share the same bidirectional redox sensitivity unknown
  15. 2024 Medium

    Two studies expanded MMP9 biology into ferroptosis and tumor microenvironment remodeling: MMP9 was found to interact with GPX4 and modulate iron metabolism to drive ferroptosis, and the dysadherin–MMP9 axis was shown to activate cancer-associated fibroblasts and remodel the immunosuppressive microenvironment.

    Evidence LC-MS/MS interactome mapping with engineered MMP9 construct and GPX4 activity assays; co-IP/knockout rescue in humanized mouse model for dysadherin–MMP9

    PMID:39252956 PMID:39613801

    Open questions at the time
    • MMP9–GPX4 interaction mechanism (catalytic cleavage vs binding-mediated inhibition) not distinguished
    • Ferroptosis findings from single lab with engineered construct require independent replication
    • Dysadherin–MMP9 binding interface not structurally characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of full-length MMP9 activation and substrate selection, the relative in vivo contributions of catalytic versus non-catalytic (PEX domain) functions, and whether MMP9-driven ferroptosis and intracellular roles represent physiologically relevant activities or artifacts of overexpression systems.
  • No high-resolution structure of full-length proMMP9 in complex with activators or substrates
  • Catalytic vs PEX-mediated non-catalytic signaling contributions not genetically separated in vivo
  • Intracellular MMP9 substrates (tubulins, crystallins) lack in vivo validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 4
Localization
GO:0031012 extracellular matrix 5 GO:0005576 extracellular region 4 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1474244 Extracellular matrix organization 6 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-109582 Hemostasis 2 R-HSA-1266738 Developmental Biology 2
Partners
ADAM15CD44LCN2LOXL2MMP3RECKTHBS1TIMP1
Complex memberships
LCN2/LOXL2/MMP9 ternary complexMMP-9/NGAL (LCN2) complexproMMP-9/TIMP-1 complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 MMP9 (92-kDa type IV collagenase/gelatinase B) was first characterized as a metalloprotease secreted by SV40-transformed human lung fibroblasts, normal human alveolar macrophages, monocytic U937 cells, fibrosarcoma HT1080 cells, and keratinocytes. The preproenzyme (predicted Mr 78,426) contains a 19-amino-acid signal peptide and is secreted as a 92-kDa glycosylated proenzyme. It forms a noncovalent complex with TIMP and can be activated by organomercurials, resulting in removal of 73 amino acids from the NH2-terminus. The active enzyme degrades native types IV and V collagen. Five domains were identified: amino-terminal, zinc-binding, fibronectin-like collagen-binding, carboxyl-terminal hemopexin-like, and a unique proline-rich domain homologous to alpha2(V) collagen. Protein purification, NH2-terminal sequencing, substrate digestion assays, inhibitor complex analysis The Journal of biological chemistry High 2551898
1992 MMP-3 (stromelysin) activates proMMP-9 through a stepwise mechanism: MMP-3 first cleaves proMMP-9 at the Glu40-Met41 bond in the propeptide to generate an 86-kDa intermediate, then cleaves Arg87-Phe88 to yield an active 82-kDa form. This was the first demonstration of zymogen activation of one MMP family member by another. In vitro activation assay, NH2-terminal sequencing, alpha2-macroglobulin binding studies The Journal of biological chemistry High 1371271
1992 ProMMP-9 purified from HT1080 fibrosarcoma cells can be activated by 4-aminophenylmercuric acetate (yielding Mr 83,000 intermediate then Mr 67,000 active form), as well as by cathepsin G, trypsin, alpha-chymotrypsin, and MMP-3 (stromelysin 1), but not by plasmin, leukocyte elastase, plasma kallikrein, thrombin, or MMP-1. HOCl partially activates the zymogen. TIMP-1 complexed with proMMP-9 inhibits conversion of the intermediate to the active species. Active MMP-9 degrades type I gelatin rapidly and also cleaves native collagens (alpha2 chain of type I, types III, IV, and V) at non-denaturing temperatures. Protein purification, activation assays, immunoblot, substrate digestion assays The Journal of biological chemistry High 1400481
1993 The MMP9 gene promoter contains three functionally important motifs — AP-1, NF-κB, and Sp-1 binding sites — that positively contribute to induction by TPA and TNFα. The AP-1 site is indispensable but requires synergistic cooperation with either the NF-κB or Sp-1 site for full induction. TNFα rapidly induces nuclear factors binding to AP-1 and κB elements in OST cells. Promoter deletion/mutation analysis with luciferase reporter, EMSA/nuclear factor binding assays Oncogene High 8426746
1998 MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. In MMP-9-null mice, apoptosis, vascularization, and ossification in the growth plate are delayed, causing progressive growth plate lengthening (~8x normal). Bone marrow transplantation with wild-type cells rescues vascularization and ossification, identifying bone-marrow-derived 'chondroclasts' as the relevant MMP-9-expressing cell population. Growth plates from null mice show delayed release of an angiogenic activator in culture, establishing MMP-9 as a controller of angiogenesis. Gene knockout (null mutation), bone marrow transplantation rescue, histology, in vitro organ culture Cell High 9590175
1998 RECK, a membrane-anchored glycoprotein with EGF-like repeats and serine-protease inhibitor-like domains, suppresses MMP-9 secretion in malignant cells and directly binds to and inhibits MMP-9 proteolytic activity. Restored RECK expression in malignant cells reduces MMP-9 secretion and invasive activity. cDNA expression screening, invasion assay, purified protein binding and inhibition assays, conditioned medium analysis Proceedings of the National Academy of Sciences of the United States of America High 9789069
2000 CD44 provides a cell surface docking receptor for proteolytically active MMP-9, and cell surface localization of MMP-9 (via CD44) is required for its ability to promote tumor invasion and angiogenesis. MMP-9 (and MMP-2) proteolytically cleave latent TGF-beta, providing a novel mechanism for TGF-beta activation. MMP-9 localization to normal keratinocyte surfaces is also CD44-dependent and can activate latent TGF-beta. Co-immunoprecipitation, cell surface localization assays, in vitro TGF-beta cleavage assay, tumor invasion and angiogenesis models Genes & development High 10652271
2000 MMP-9 is predominantly expressed by inflammatory cells (neutrophils, macrophages, mast cells) rather than by neoplastic keratinocytes in a mouse model of multistage skin carcinogenesis driven by HPV16. MMP-9-null transgenic mice show reduced keratinocyte hyperproliferation at all neoplastic stages and decreased incidence of invasive tumors. Bone marrow chimeras expressing MMP-9 only in hematopoietic cells reconstitute MMP-9-dependent contributions to carcinogenesis, establishing that inflammatory cell-derived MMP-9 promotes tumor progression. Transgenic knockout mouse, bone marrow transplantation chimeras, histopathology, tumor incidence analysis Cell High 11081634
2000 MMP-9 (neutrophil gelatinase B) cleaves IL-8(1-77) at the aminoterminus to generate IL-8(7-77), resulting in a 10- to 27-fold higher potency in neutrophil activation (intracellular Ca2+ increase, gelatinase B secretion, chemotaxis). This enhancement correlates with increased binding to neutrophils and enhanced signaling through CXCR1 but not CXCR2. MMP-9 also degrades CTAP-III, PF-4, and GRO-alpha but leaves RANTES and MCP-2 intact, demonstrating substrate specificity for CXC chemokine processing. In vitro enzyme cleavage assays, calcium flux assay, chemotaxis assay, receptor binding assay Blood High 11023497
2001 MMP-9 and NGAL (neutrophil gelatinase-associated lipocalin) form a ~125-kDa complex detectable in urine. NGAL protects MMP-9 from degradation in a dose-dependent manner, thereby preserving MMP-9 enzymatic activity. The complex can be reconstituted in vitro by mixing recombinant MMP-9 and NGAL. Substrate gel electrophoresis, immunoprecipitation, Western blot, in vitro reconstitution, cell culture overexpression The Journal of biological chemistry High 11486009
2001 Thrombospondin-1 (TSP1) suppresses in vivo activation of proMMP-9 and in vitro enzymatic activation of proMMP-9 is suppressed by purified TSP1. Absence of TSP1 in mammary tumor-prone mice results in higher levels of active MMP-9 and increased VEGF/VEGFR2 association, implicating TSP1 as an endogenous regulator of MMP-9 activation. Transgenic mouse model (TSP1 knockout and overexpression), in vitro proMMP9 activation assay with purified TSP1, VEGFR2 co-precipitation Proceedings of the National Academy of Sciences of the United States of America High 11606713
2002 MMP-9 induced in bone marrow (BM) cells releases soluble Kit-ligand (sKitL) from the bone marrow niche, enabling transfer of hematopoietic and endothelial stem cells from quiescent to proliferative niches. BM ablation induces SDF-1, which upregulates MMP-9 expression, causing shedding of sKitL and recruitment of c-Kit+ stem/progenitors. In MMP-9-/- mice, sKitL release and HSC motility are impaired; exogenous sKitL restores hematopoiesis and survival. MMP-9 knockout mice, BM ablation, SDF-1 stimulation, exogenous sKitL rescue, stem cell mobilization assays Cell High 12062105
2002 MMP-9 and MMP-2 work in concert to produce aortic aneurysms in a mouse model; neither MMP-9KO nor MMP-2KO mice develop aneurysms following CaCl2 application. Reinfusion of wild-type macrophages into MMP-9KO mice reconstitutes AAA formation, but not in MMP-2KO mice, indicating macrophage-derived MMP-9 and mesenchymal cell MMP-2 play distinct and cooperative roles. Genetic knockout mice, experimental AAA induction, macrophage reinfusion rescue experiment The Journal of clinical investigation High 12208863
2002 MMP-9 and MMP-2 are shed by endothelial cells as components of membrane vesicles (300–600 nm) in both pro- and active forms. Shedding is stimulated by serum and angiogenic factors FGF-2 and VEGF. Shed vesicles stimulate autocrine endothelial cell invasion through Matrigel and cord formation, establishing vesicle-based MMP secretion as a mechanism for focalized proteolytic activity during angiogenesis. Ultrastructural analysis, zymography, Western blot, immunogold labeling, invasion and morphogenesis assays The American journal of pathology High 11839588
2002 MMP9 is specifically induced in premetastatic lung endothelial cells and macrophages by distant primary tumors via VEGFR-1/Flt-1 tyrosine kinase signaling, and this induction significantly promotes lung-specific metastasis. Deletion of VEGFR-1 TK or MMP9 markedly reduces lung metastasis in mice. Genetic deletion of VEGFR-1 TK and MMP9 in mice, experimental metastasis assays, immunohistochemistry in human samples Cancer cell High 12398893
2003 tPA upregulates MMP-9 via LRP (low-density lipoprotein receptor-related protein) signaling in brain endothelial cells. RNAi knockdown of LRP abolished tPA-induced MMP-9 upregulation. MMP-9 levels were lower in tPA-knockout mice after focal ischemia, demonstrating that tPA-LRP signaling drives MMP-9-mediated neurovascular matrix degradation in stroke. RNAi knockdown, tPA knockout mice, focal ischemia model, cell culture MMP-9 measurement Nature medicine High 12960961
2003 Hepatic injury induces MMP-9 activity in the liver, which together with SDF-1 and HGF promotes recruitment of human CD34+ hematopoietic progenitors to the liver. MMP-9 activity is induced by irradiation or inflammation and contributes to CXCR4 upregulation and SDF-1-mediated progenitor homing. In vivo mouse liver injury model, MMP-9 activity measurement, CXCR4 neutralization, NOD/SCID engraftment assay The Journal of clinical investigation Medium 12865405
2006 Cited2, a CBP/p300-binding transcriptional co-activator, physically associates with Smad2 and Smad3 (confirmed by co-IP, mammalian two-hybrid, and GST pull-down) and enhances TGF-β-mediated upregulation of MMP9. p300 further enhances the Cited2-Smad3 interaction. Chromatin immunoprecipitation showed Cited2 and Smad3 are recruited to the MMP9 promoter upon TGF-β stimulation. Knockdown of Cited2 in MDA-MB-231 cells attenuates TGF-β-mediated MMP9 upregulation and cell invasion. Co-IP, mammalian two-hybrid, GST pull-down, ChIP, luciferase reporter, siRNA knockdown, invasion assay Oncogene High 16619037
2007 Human neutrophils uniquely release TIMP-free proMMP-9 from their granules, which upon activation is a potent proangiogenic stimulus at subnanogram levels on the chick chorioallantoic membrane. TIMP-1 complexation abolishes the proangiogenic activity of neutrophil proMMP-9, demonstrating that the TIMP-free status and catalytic activity of the activated enzyme are both required for the angiogenic response. Granule purification, in vivo chick CAM angiogenesis assay, stoichiometric TIMP-1 complexation, MMP activity assays Proceedings of the National Academy of Sciences of the United States of America High 18077379
2008 MMP-9-positive neutrophil infiltration is associated with blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke. The cleaved 85-kDa active form of MMP-9 is elevated in hemorrhagic areas, and laser capture microdissection confirmed high MMP-9 in microvessel endothelium and surrounding neutrophils at hemorrhagic sites. Gelatin zymography, immunohistochemistry, laser capture microdissection, human stroke tissue analysis Stroke Medium 18323498
2011 Concomitant deficiency of MMP9 and uPA (but not tPA alone or uPAR alone) impairs normal gestation in mice. Combined lack of MMP9 and uPA exacerbates effects on bone growth and shows additive effects on cutaneous wound healing. MMP9 deficiency in wounds leads to compensatory upregulation of uPA activity, revealing a functional dependency between MMP9 and uPA in tissue repair. Double-gene knockout mice (MMP9/uPA, MMP9/tPA, MMP9/uPAR), gestation analysis, bone measurement, wound healing assay, uPA activity measurement Developmental biology High 21802414
2013 MMP-9 is a multidomain enzyme with hemopexin (PEX), O-glycosylated, and catalytic domains supporting attachment, articulation, and catalysis, respectively. ProMMP-9 activation involves MMP-3 priming; meprins may destabilize the aminoterminus–fibronectin repeat interaction, and autocatalytic activation can occur when molecules bind the catalytic site displacing the cysteine from the zinc ion. The substrate repertoire extends from ECM to membrane-bound and intracellular proteins including crystallins, tubulins, and actins. The PEX domain exerts non-catalytic anti-apoptotic signaling. MMP-9 oligomers and heteromers (e.g., with NGAL) have distinct biological properties. Review synthesizing structural biology, degradomics, knockout mouse phenotype analysis, biochemical activation studies Critical reviews in biochemistry and molecular biology High 23547785
2013 ADAM17 mediates LPS-induced MMP9 expression in lung epithelial cells (A549) via TNF-α/NF-κB signaling. Lentiviral RNAi knockdown of ADAM17 inhibits TNF-α shedding into supernatants, reduces IκBα phosphorylation and p65 phosphorylation, and decreases MMP9 expression in response to LPS, placing ADAM17 upstream of MMP9 in this pathway. Lentiviral RNAi, pharmacological NF-κB inhibitor (PDTC), TNFR1 blocking peptide, Western blot, ELISA PloS one Medium 23341882
2014 TRPV4 activation provides a Ca2+ source necessary for rapid release and activation of MMP2 and MMP9 in intact mouse lung, contributing to septal barrier disruption and lung injury. TRPV4-/- lungs do not show MMP activation upon agonist treatment, and pharmacological MMP2/9 blockade (SB-3CT) protects against TRPV4-induced injury. TIMP-2 levels are decreased in TRPV4-injured lungs, increasing availability of active MMPs. TRPV4 knockout mice, TRPV4 agonist perfusion, Western blot for active MMP isoforms, pharmacological MMP inhibition, lung injury assessment American journal of physiology. Lung cellular and molecular physiology Medium 25150065
2014 Glioma cells induce MMP9 expression in microglia/macrophages via Toll-like receptor 2/6 (TLR2/6) signaling and p38 MAPK. TLR2-deficient mice show attenuated microglial MMP9 upregulation in experimental gliomas. Minocycline and p38 MAPK antagonists attenuate MMP9 and TLR2 upregulation in vitro. Glioma supernatant also upregulates TLR2 expression in microglia. TLR2-knockout mice, experimental glioma model, in vitro macrophage stimulation, minocycline and p38 inhibitor treatment International journal of cancer Medium 24752463
2014 ADAM15 upregulates MMP9 expression in lung cancer cells via MEK-ERK pathway activation and also proteolytically cleaves and activates pro-MMP9 directly in vitro, while interacting with MMP9 in vivo. Knockdown of MMP9 attenuates the invasive promotion by ADAM15 overexpression, placing ADAM15 as both an upstream regulator and direct activator of MMP9. shRNA knockdown, co-immunoprecipitation, in vitro pro-MMP9 cleavage assay, MEK-ERK inhibitor treatment, invasion assays Oncology reports Medium 26323669
2015 Endothelin-1 controls ventricular superoxide levels, which regulate MMP9 expression. In endothelin-1 hypomorphic mice, increased ventricular superoxide drives MMP9 overexpression, leading to reduced ventricular stiffness and dilated cardiomyopathy. A superoxide dismutase mimetic normalizes superoxide levels and reduces MMP9 overexpression, substantially improving cardiac function. Genetic ablation of MMP9 also improves cardiac function (without reducing superoxide), placing MMP9 downstream of superoxide in cardiac remodeling. Hypomorphic/hypermorphic allele mouse model, Cre-loxP switching, SOD mimetic treatment, MMP9 knockout, cardiac functional measurements Proceedings of the National Academy of Sciences of the United States of America High 25848038
2015 ATP6V1H deficiency in zebrafish dramatically increases mmp9 (and mmp13) expression, leading to reduced calcified bone cells and bone defects. Treatment of mutant embryos with MMP9/MMP13 small molecule inhibitors significantly restores bone mass, placing MMP9 downstream of V-ATPase activity in a pathway controlling bone formation. CRISPR/Cas9 knockout in zebrafish, pharmacological MMP inhibition rescue, skeletal staining, gene expression analysis PLoS genetics Medium 28158191
2020 MMP9 promotes mesenchymal transition of pancreatic ductal adenocarcinoma cells via cleavage and activation of PAR1 (protease-activated receptor 1). Macrophage-secreted MMP9 was identified as the relevant PAR1 agonist by protease profiling and PAR1 cleavage assays. Inhibition of MMP9 and/or PAR1 limits macrophage-driven mesenchymal transition and reduces tumor cell survival against macrophage anti-tumor activity. PAR1 cleavage assays, MMP9/PAR1 inhibitors, medium transfer experiments, siRNA knockdown of ZEB1, tissue microarray correlation Cellular oncology (Dordrecht, Netherlands) Medium 32809114
2020 Constitutive expression of MMP9 in the colonic epithelium (TgM9 mice) reduces reactive oxygen species, decreases DNA damage, and increases mismatch repair gene expression during colitis-associated cancer, suppressing tumor development via an 'MMP9-Notch1-ARF-p53 axis'. MMP9 siRNA-loaded nanoparticles that silence MMP9 in the colon increase ROS and DNA damage, confirming MMP9's tumor suppressor role in this context. Transgenic mouse model, siRNA nanoparticle knockdown, ROS measurement, DNA damage assays, mismatch repair gene expression Cell death & disease Medium 32943603
2021 Glucocorticoid-mediated stress enhances secretory autophagy via the stress-responsive co-chaperone FKBP51 (FK506-binding protein 51), leading to MMP9 secretion. Stress-enhanced MMP9 secretion increases cleavage of proBDNF to its mature form (mBDNF), as demonstrated by cellular assays and in vivo microdialysis, linking the stress response to synaptic plasticity via MMP9-mediated proBDNF processing. Cellular secretory autophagy assays, in vivo microdialysis, FKBP51 manipulation, proBDNF/mBDNF cleavage assays Nature communications Medium 34330919
2021 PPARγ downregulates MMP9 expression after intracerebral hemorrhage by inhibiting NF-κB. Activation of PPARγ with rosiglitazone decreases NF-κB and MMP9; NF-κB inhibition (JSH-23) also suppresses MMP9 with limited effect on PPARγ. Protein co-IP confirmed direct interactions of NF-κB with PPARγ and MMP9 gene, and ChIP confirmed NF-κB binding to MMP9 promoter. In vivo and in vitro PPARγ agonist/antagonist treatment, NF-κB inhibitor, co-IP, ChIP, Western blot Neuroscience letters Medium 33636289
2021 Macrophage migration through ECM requires both MMP9-mediated degradation (mesenchymal migration mode) and Rac GTPase signaling. Inhibition of MMPs or Rac abolishes ECM degradation by macrophages and suppresses their ability to mobilize hematopoietic stem/progenitor cells in zebrafish embryos, demonstrating that MMP9-dependent mesenchymal migration is functionally linked to HSPC mobilization. Live imaging in zebrafish embryos, MMP inhibitors, Rac inhibitors, morphometric analysis, HSPC mobilization assay Scientific reports Medium 33980872
2022 HOCl (generated by an enzymatic MPO/H2O2/Cl- system) activates proMMP9 via oxidation of the cysteine switch mechanism, as demonstrated by fluorescence activity assays and gel zymography. Low nanomolar-to-low micromolar concentrations of chloramines formed from amino acids, serum albumin, and ECM proteins (laminin, fibronectin) also activate proMMP9, and this activation is diminished by the competitive HOCl-reactive species methionine. High HOCl concentrations inactivate active MMP9, establishing a concentration-dependent bidirectional redox regulation. Fluorescence activity assays, gel zymography, MPO enzymatic system, chloramine preparation, competitive inhibition with methionine Antioxidants (Basel, Switzerland) High 36009335
2023 LCN2, LOXL2, and MMP9 form a ternary protein complex: LCN2-LOXL2 and LCN2-MMP9 interactions occur both intracellularly and extracellularly, while LOXL2-MMP9 interactions only occur intracellularly. The LCN2/LOXL2/MMP9 complex enhances ECM proteolytic activity (fibronectin and Matrigel degradation), filopodia formation, microfilament rearrangement via profilin-1 upregulation, SPOCK1 expression, and FAK/AKT/GSK3β pathway activation. Protein-protein interaction assays (co-IP, PLA), co-overexpression functional studies, matrix degradation assays, in vivo tumor models, pathway analysis Molecular oncology Medium 37753805
2024 Active MMP9 drives ferroptosis by directly interacting with GPX4 (glutathione peroxidase 4) and glutathione reductase, reducing GPX4 expression and activity. MMP9 suppresses key transcription factors (SP1, CREB1, NRF2, FOXO3, ATF4) and GPX1 and FSP1, disrupting cellular redox balance. MMP9 also regulates iron metabolism by modulating iron import, storage, and export through a network of protein interactions. LC-MS/MS identified 83 proteins interacting with MMP9 at subcellular levels implicated in ferroptosis regulation. Engineered MMP9 construct without collagenase activity, LC-MS/MS protein interaction mapping, GPX4 activity assays, transcription factor expression analysis, integrated pathway analysis iScience Medium 39252956
2024 Dysadherin directly targets MMP9, and the dysadherin/MMP9 axis enhances ECM proteolytic activity, promotes CRC cell invasiveness, activates cancer-associated fibroblasts, and orchestrates ECM remodeling. In a humanized mouse model, dysadherin knockout reduces immunosuppressive and proangiogenic microenvironment, and these effects are reversed by MMP9 overexpression. Co-IP/direct targeting assays, MMP9 overexpression rescue, dysadherin knockout mouse model, ECM proteolytic activity assays, humanized mouse model Nature communications Medium 39613801
1996 The 92-kDa type IV collagenase gene (CLG4B/MMP9) was remapped from human chromosome 16 to chromosome 20 using somatic cell hybrid panel screening, FISH, and linkage analysis with a newly identified polymorphism. Somatic cell hybrid panel, FISH, linkage analysis Cytogenetics and cell genetics High 8978762
2020 MMP-9 mediates Syndecan-4 (Sdc4) shedding under osteoarthritis conditions. MMP-9 (but not MMP-2) is elevated in cartilage, synovial membrane, and synovial fluid of OA patients and correlates with shed Sdc4 levels. siRNA knockdown and pharmacological inhibition of MMP-9 decrease shed Sdc4 in vitro. Increased Sdc4 shedding results in reduced ERK phosphorylation upon IL-1β stimulation, desensitizing chondrocytes to IL-1 signaling. siRNA knockdown, MMP inhibitors, ELISA, IHC, RT-qPCR, Western blot (pERK/ERK) Osteoarthritis and cartilage Medium 33246160
2021 MMP-9 interacts with CD44 via its hemopexin (PEX) domain on the cell surface, while the catalytic domain cleaves CD44. A bispecific inhibitor (C9-PEX) simultaneously targeting both MMP9 catalytic and PEX domains and CD44 reduces MMP9 cellular levels, interferes with MMP9 homodimerization, and inhibits activation of the downstream MAPK/ERK pathway, demonstrating functional roles of both MMP9 domains in cancer cell invasiveness. Yeast surface display engineering, bispecific inhibitor design, cell-based functional assays for invasion, MMP9 dimerization assays, MAPK/ERK pathway analysis The Biochemical journal Medium 33600567

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 3725 23128233
1999 Matrix metalloproteinases. The Journal of biological chemistry 3561 10419448
2000 Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes & development 1558 10652271
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1998 MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1455 9590175
2002 Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 1354 12062105
2020 The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. International journal of molecular sciences 1233 33419373
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1989 SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. The Journal of biological chemistry 1079 2551898
2000 MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 1076 11081634
2002 Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. The Journal of clinical investigation 891 12208863
2002 MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer cell 713 12398893
1993 Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 712 8426746
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2013 Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Critical reviews in biochemistry and molecular biology 622 23547785
2003 Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 612 12668489
2001 The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL. The Journal of biological chemistry 579 11486009
1992 Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. The Journal of biological chemistry 566 1371271
2000 Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood 546 11023497
2003 HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver. The Journal of clinical investigation 502 12865405
2007 Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 488 18077379
2002 Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. The American journal of pathology 470 11839588
2008 MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke 469 18323498
1992 Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. The Journal of biological chemistry 460 1400481
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1998 Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proceedings of the National Academy of Sciences of the United States of America 405 9789069
2003 Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator. Nature medicine 384 12960961
2001 Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proceedings of the National Academy of Sciences of the United States of America 380 11606713
2016 MMP-9 in translation: from molecule to brain physiology, pathology, and therapy. Journal of neurochemistry 317 26525923
2012 Matrix metalloproteinases in diabetic retinopathy: potential role of MMP-9. Expert opinion on investigational drugs 139 22519597
2021 Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion. Nature communications 105 34330919
1999 Expression of Mmp-9 and related matrix metalloproteinase genes during axolotl limb regeneration. Developmental dynamics : an official publication of the American Association of Anatomists 105 10474160
2014 Glioma-associated microglial MMP9 expression is upregulated by TLR2 signaling and sensitive to minocycline. International journal of cancer 99 24752463
2014 MiRNA-181c inhibits EGFR-signaling-dependent MMP9 activation via suppressing Akt phosphorylation in glioblastoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 98 24867100
2006 Cited2 modulates TGF-beta-mediated upregulation of MMP9. Oncogene 93 16619037
2020 Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival. Breast cancer research and treatment 92 32445177
2011 Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer. Journal of gastroenterology and hepatology 79 21261731
2016 The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9. PloS one 77 26872030
2016 MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma. Aging 75 27115178
2014 SEMA4b inhibits MMP9 to prevent metastasis of non-small cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 65 25095981
2014 Role of MMP2 and MMP9 in TRPV4-induced lung injury. American journal of physiology. Lung cellular and molecular physiology 64 25150065
2014 DLK1 promotes lung cancer cell invasion through upregulation of MMP9 expression depending on Notch signaling. PloS one 63 24621612
2021 Infarct in the Heart: What's MMP-9 Got to Do with It? Biomolecules 61 33805901
2021 Dendrobine attenuates osteoclast differentiation through modulating ROS/NFATc1/ MMP9 pathway and prevents inflammatory bone destruction. Phytomedicine : international journal of phytotherapy and phytopharmacology 57 34801352
2020 Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer. Cell death & disease 57 32943603
2019 Tenascin-cmediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma. Cell death & disease 56 31754182
2019 Macrophage-secreted TSLP and MMP9 promote bleomycin-induced pulmonary fibrosis. Toxicology and applied pharmacology 52 30653976
2015 Expression of MMP-9 and VEGF in meningiomas and their correlation with peritumoral brain edema. BioMed research international 51 25821815
2020 Macrophage-secreted MMP9 induces mesenchymal transition in pancreatic cancer cells via PAR1 activation. Cellular oncology (Dordrecht, Netherlands) 50 32809114
2021 Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2. Theranostics 48 34093860
2020 MMP-9 mediated Syndecan-4 shedding correlates with osteoarthritis severity. Osteoarthritis and cartilage 48 33246160
2017 ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13. PLoS genetics 48 28158191
2015 Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade. Proceedings of the National Academy of Sciences of the United States of America 47 25848038
2002 Control of MMP-9 expression at the maternal-fetal interface. Journal of reproductive immunology 44 12062817
2017 Synergistic effect of collagenase-1 (MMP1), stromelysin-1 (MMP3) and gelatinase-B (MMP9) gene polymorphisms in breast cancer. PloS one 42 28961241
2024 The dysadherin/MMP9 axis modifies the extracellular matrix to accelerate colorectal cancer progression. Nature communications 41 39613801
2014 CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway. Molecular carcinogenesis 40 24664993
2014 Ablation of MMP9 gene ameliorates paracellular permeability and fibrinogen-amyloid beta complex formation during hyperhomocysteinemia. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 39 24865997
2012 MMP-9 and uPAR regulated glioma cell migration. Cell adhesion & migration 37 23076139
2020 Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer. Oncogene 36 32655131
2017 P2X7 receptor antagonism modulates IL-1β and MMP9 in human atherosclerotic vessels. Scientific reports 36 28687781
2016 HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9. Molecular medicine reports 35 27573865
2024 MMP-9 responsive hydrogel promotes diabetic wound healing by suppressing ferroptosis of endothelial cells. Bioactive materials 34 39386223
2020 USP19 Enhances MMP2/MMP9-Mediated Tumorigenesis in Gastric Cancer. OncoTargets and therapy 34 32904569
2018 Cigarette smoke-induced RANKL expression enhances MMP-9 production by alveolar macrophages. International journal of chronic obstructive pulmonary disease 33 30587964
2014 Anti-inflammatory macrophages activate invasion in pancreatic adenocarcinoma by increasing the MMP9 and ADAM8 expression. Medical oncology (Northwood, London, England) 32 24526468
2021 Elevated expression of MMP8 and MMP9 contributes to diabetic osteoarthritis progression in a rat model. Journal of orthopaedic surgery and research 31 33468174
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
2013 CD147, MMP9 expression and clinical significance of basal-like breast cancer. Medical oncology (Northwood, London, England) 31 23292863
2021 TPM3 mediates epithelial-mesenchymal transition in esophageal cancer via MMP2/MMP9. Annals of translational medicine 30 34532475
2021 Muscone derivative ZM-32 inhibits breast tumor angiogenesis by suppressing HuR-mediated VEGF and MMP9 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 33450490
2015 ADAM15 targets MMP9 activity to promote lung cancer cell invasion. Oncology reports 29 26323669
2015 DNA Methylation of MMP9 Is Associated with High Levels of MMP-9 Messenger RNA in Periapical Inflammatory Lesions. Journal of endodontics 29 26549219
2019 Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 31366234
2011 MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation. Molecular carcinogenesis 28 22121096
2010 Polymorphisms in MMP-9 and TIMP-2 in Chinese patients with varicose veins. The Journal of surgical research 28 21195432
2013 Role of site-specific DNA demethylation in TNFα-induced MMP9 expression in keratinocytes. Journal of molecular endocrinology 27 23417766
2020 L-theanine suppresses the metastasis of prostate cancer by downregulating MMP9 and Snail. The Journal of nutritional biochemistry 25 33249185
2017 Expression of NGF, GDNF and MMP-9 in prostate carcinoma. Pathology, research and practice 25 28237042
2015 Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis. Biochemical and biophysical research communications 24 25600809
2015 CD151 knockdown inhibits osteosarcoma metastasis through the GSK-3β/β-catenin/MMP9 pathway. Oncology reports 24 26707073
2007 Cholesterol inhibits MMP-9 expression in human epidermal keratinocytes and HaCaT cells. FEBS letters 24 17643435
2012 VEGF and MMP-9: biomarkers for canine lymphoma. Veterinary and comparative oncology 23 22489798
2023 A protein complex of LCN2, LOXL2 and MMP9 facilitates tumour metastasis in oesophageal cancer. Molecular oncology 22 37753805
2017 Sirtuin 6 contributes to migration and invasion of osteosarcoma cells via the ERK1/2/MMP9 pathway. FEBS open bio 22 28904859
2015 Dual-Functions of miR-373 and miR-520c by Differently Regulating the Activities of MMP2 and MMP9. Journal of cellular physiology 22 25545756
2007 Fetal MMP2/MMP9 polymorphisms and intrauterine growth restriction risk. Journal of reproductive immunology 22 17367869
2021 Simultaneous targeting of CD44 and MMP9 catalytic and hemopexin domains as a therapeutic strategy. The Biochemical journal 21 33600567
2022 Activation and Inhibition of Human Matrix Metalloproteinase-9 (MMP9) by HOCl, Myeloperoxidase and Chloramines. Antioxidants (Basel, Switzerland) 20 36009335
2021 PPARγ activation suppresses the expression of MMP9 by downregulating NF-κB post intracerebral hemorrhage. Neuroscience letters 20 33636289
2020 Expression of RSK4, CD44 and MMP-9 is upregulated and positively correlated in metastatic ccRCC. Diagnostic pathology 20 32209138
2016 MMP2 and MMP9 associate with crescentic glomerulonephritis. Clinical kidney journal 20 28584626
2013 ADAM17 mediates MMP9 expression in lung epithelial cells. PloS one 20 23341882
2021 Macrophage morphological plasticity and migration is Rac signalling and MMP9 dependant. Scientific reports 19 33980872
2020 MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease. Journal of cellular physiology 19 32052443
2014 Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading. Pathology, research and practice 19 25441661
2011 Expression of MMP-2 and MMP-9 in retinoblastoma and their significance. International journal of ophthalmology 19 22553708
1996 Reassignment of the 92-kDa type IV collagenase gene (CLG4B) to human chromosome 20. Cytogenetics and cell genetics 19 8978762
2022 Evaluation of the matrix metalloproteinase 9 (MMP9) inhibitor Andecaliximab as an Anti-invasive therapeutic in Head and neck squamous cell carcinoma. Oral oncology 18 35803110
2022 Lactobacilli metabolites restore E-cadherin and suppress MMP9 in cervical cancer cells. Current research in toxicology 18 36176311
2011 Concomitant lack of MMP9 and uPA disturbs physiological tissue remodeling. Developmental biology 18 21802414
2019 Effect of MMP-9 gene knockout on retinal vascular form and function. Physiological genomics 17 31709889
2021 Expression and clinical significance of MMP-9 and P53 in lung cancer. European review for medical and pharmacological sciences 16 33629306
2020 Ceramide induces MMP-9 expression through JAK2/STAT3 pathway in airway epithelium. Lipids in health and disease 16 32829707
2018 MiR-5692a promotes the invasion and metastasis of hepatocellular carcinoma via MMP9. European review for medical and pharmacological sciences 16 30070322
2012 Association of the MMP9 gene with childhood cedar pollen sensitization and pollinosis. Journal of human genetics 16 22237587
2011 Gelatinases (MMP2 and MMP9) in swine antral follicle. BioFactors (Oxford, England) 16 21488134
2023 Fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) as predictive values for nonalcoholic steatohepatitis (NASH). Lipids in health and disease 15 36609276
2022 Exosomes from EGFR-Mutated Adenocarcinoma Induce a Hybrid EMT and MMP9-Dependant Tumor Invasion. Cancers 15 35954442
2021 MMP-9 Signaling Pathways That Engage Rho GTPases in Brain Plasticity. Cells 15 33467671
2021 Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages. Frontiers in pharmacology 15 33959010
2014 Expression and significance of MMP-9 and MDM2 in the oncogenesis of lung cancer in rats. Asian Pacific journal of tropical medicine 15 25063292
2021 Computational study of effective matrix metalloproteinase 9 (MMP9) targeting natural inhibitors. Aging 14 34607974
2018 Expression and correlation of MMP-9, VEGF, and p16 in infantile hemangioma. European review for medical and pharmacological sciences 14 30070315
2016 FoxO3a mediates glioma cell invasion by regulating MMP9 expression. Oncology reports 14 27633065
2024 MMP9 drives ferroptosis by regulating GPX4 and iron signaling. iScience 13 39252956
2020 microRNA-204-5p Participates in Atherosclerosis Via Targeting MMP-9. Open medicine (Warsaw, Poland) 13 32266319
2017 Association of MMP-9 gene polymorphisms with nephrolithiasis patients. Journal of clinical laboratory analysis 13 28205286
2017 Immunohistochemical expression of TGF-β1 and MMP-9 in periapical lesions. Brazilian oral research 13 28678970
2014 Resistance of MMP9 and TIMP1 to endotoxin tolerance. Pathogens and disease 13 25951835
2023 Characterization of Active MMP9 in Chronic Inflammatory Diseases Using a Novel Anti-MMP9 Antibody. Antibodies (Basel, Switzerland) 12 36810514
2019 Density-dependent ERK MAPK expression regulates MMP-9 and influences growth. Molecular and cellular biochemistry 12 30689107
2019 Natriuretic peptide receptor a promotes breast cancer development by upregulating MMP9. American journal of cancer research 12 31392078
2017 Pregnancy and parturition negatively impact vaginal angle and alter expression of vaginal MMP-9. American journal of obstetrics and gynecology 12 29155140
2012 Collagen IV and MMP-9 expression in hypertrophic gingiva during orthodontic treatment. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 12 22395516
2009 Polyclonal immunoglobulins (IVIg) induce expression of MMP-9 in microglia. Journal of neuroimmunology 12 19833395
2024 Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway. Chinese journal of integrative medicine 11 38212502
2023 Hydrogen attenuates postoperative pain through Trx1/ASK1/MMP9 signaling pathway. Journal of neuroinflammation 11 36737785