Affinage

MMP10

Stromelysin-2 · UniProt P09238

Length
476 aa
Mass
54.2 kDa
Annotated
2026-04-28
95 papers in source corpus 35 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MMP-10 (stromelysin-2) is a secreted zinc-dependent metalloprotease that degrades extracellular matrix components, activates other MMPs, and modulates macrophage inflammatory polarization to orchestrate tissue remodeling, repair, and immune resolution. MMP-10 cleaves laminin-5 and fibronectin to promote keratinocyte and endothelial cell migration, activates proMMP-1 to drive capillary tube regression, and processes proMMP-9 in macrophages during fracture healing (PMID:15371548, PMID:15870107, PMID:34173256). In macrophages, MMP-10 tempers M1 pro-inflammatory activation and promotes M2 polarization via STAT3 signaling, thereby resolving inflammation in infection, colitis, and wound healing; its absence leads to exaggerated inflammatory responses and impaired tissue repair (PMID:27316687, PMID:23044923, PMID:37844469). MMP-10 transcription is regulated by MEF2A (downstream of TGF-β/HDAC degradation), CHF1/Hey2 (via E-box repression), SOX9/Wnt/β-catenin, PPARγ, VEGF/Ets-1, NOX5/JNK/AP-1, and noncanonical NF-κB (RelB/TRIM35), and is inhibited by TIMP-1 (Ki ~1 nM) and TIMP-2, as defined by crystal structures of the catalytic domain–TIMP-1 complex (PMID:22427646, PMID:19935709, PMID:20432469, PMID:37844469, PMID:39865905).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 Medium

    Establishing that MMP-10 is a secreted, autocatalytically processed metalloprotease resolved its basic biochemical identity as a zymogen activated by prodomain removal.

    Evidence Recombinant murine MMP-10 expressed in COS cells secreted and processed by APMA activation

    PMID:9427548

    Open questions at the time
    • Full substrate repertoire undefined
    • Physiological activators in vivo not identified
    • Single recombinant system
  2. 2004 High

    Demonstrating that MMP-10 degrades laminin-5 and controls keratinocyte migration in vivo established its first defined ECM substrate and tissue-repair function.

    Evidence In vitro degradation assay plus transgenic mice expressing constitutively active MMP-10 in keratinocytes showing aberrant wound repair

    PMID:15371548

    Open questions at the time
    • Whether MMP-10 cleaves laminin-5 at specific sites versus general degradation
    • Relative contribution versus MMP-3 in wound keratinocytes
  3. 2005 High

    Identifying serine proteases as physiological MMP-10 activators and MMP-1 as a downstream target linked MMP-10 to a proteolytic cascade driving capillary tube regression.

    Evidence siRNA knockdown and adenoviral overexpression in 3D collagen matrix tube regression assays with zymography

    PMID:15870107

    Open questions at the time
    • Which serine protease is the dominant activator in vivo
    • Whether other MMPs besides MMP-1 mediate tube regression downstream of MMP-10
  4. 2009 High

    Elucidating TGF-β–driven transcriptional induction of MMP-10 via HDAC degradation and MEF2A acetylation provided the first detailed transcriptional regulatory mechanism for MMP-10.

    Evidence Promoter-reporter assays, ChIP for MEF2A at MMP-10 promoter, siRNA knockdown of MEF2A, HDAC overexpression

    PMID:19935709

    Open questions at the time
    • Whether MEF2A regulation operates in macrophages or is limited to the cancer cell context studied
    • Identity of other transcription factors cooperating at the MMP-10 promoter
  5. 2010 High

    Showing that VEGF induces MMP-10 through Ets-1 and that MMP-10 is required for angiogenesis placed MMP-10 as a functional effector of VEGF signaling in endothelial biology.

    Evidence siRNA knockdown inhibiting migration and tube formation in vitro plus Matrigel plug angiogenesis in vivo

    PMID:20432469

    Open questions at the time
    • Direct MMP-10 substrates mediating angiogenesis not identified
    • Whether MMP-10 and MMP-3 have redundant roles in VEGF-driven angiogenesis
  6. 2011 Medium

    Identifying CHF1/Hey2 as an E-box–dependent transcriptional repressor of MMP-10 in vascular smooth muscle cells expanded the regulatory network and suggested context-dependent transcriptional control.

    Evidence Promoter-reporter assays with E-box mutagenesis, siRNA knockdown, CHF1/Hey2 knockout cells

    PMID:22079635

    Open questions at the time
    • In vivo vascular phenotype of CHF1/Hey2-driven MMP-10 derepression not tested
    • Single lab, not independently replicated
  7. 2012 High

    Solving the 1.9 Å crystal structure of the MMP-10 catalytic domain bound to TIMP-1, and measuring Ki values for TIMP-1 (~1 nM) and TIMP-2 (~6 nM), provided the structural basis for endogenous inhibition of MMP-10.

    Evidence X-ray crystallography and rigorous enzyme kinetics with multiple inhibition constant determination methods

    PMID:22427646

    Open questions at the time
    • Full-length MMP-10 structure not determined
    • In vivo relevance of TIMP-1 versus TIMP-2 selectivity not established
  8. 2012 High

    Demonstrating that MMP-10 deficiency exacerbates colitis and that bone marrow–derived MMP-10 resolves inflammation established the myeloid compartment as the critical source and immune resolution as a core function.

    Evidence Mmp10−/− mice in DSS colitis model with bone marrow transplant rescue

    PMID:23044923

    Open questions at the time
    • Direct substrate mediating colitis resolution unknown
    • Whether MMP-10 acts on immune cell recruitment or cytokine processing not distinguished
  9. 2013 High

    Showing that MMP-10 is required for macrophage migration and invasion over fibronectin provided a cell-autonomous mechanism for its immune functions.

    Evidence Mmp10−/− bone marrow-derived macrophages with reduced migration rescued by exogenous active MMP-10 protein

    PMID:23691065

    Open questions at the time
    • Fibronectin fragment(s) generated by MMP-10 not identified
    • Whether migration defect is purely proteolytic or involves signaling
  10. 2014 High

    Establishing that MMP-10 is required for skeletal muscle regeneration via VEGF/Akt signaling and CXCR4/SDF1 axis expanded its repair functions beyond wound healing to muscle and vascular contexts.

    Evidence Mmp10−/− mice with notexin injury, mdx cross, recombinant MMP-10 rescue, and SDF1/CXCR4 epistasis experiments

    PMID:24123596 PMID:24548137

    Open questions at the time
    • Direct MMP-10 substrate in muscle regeneration not identified
    • Relative contribution of MMP-10 proteolysis versus signaling modulation unclear
  11. 2016 High

    Adoptive transfer experiments proved that macrophage-derived MMP-10 moderates M1 activation and promotes M2 polarization in vivo, resolving infection-induced morbidity and establishing MMP-10 as an intrinsic macrophage polarization regulator.

    Evidence Mmp10−/− mice with Pseudomonas infection, adoptive transfer of wild-type BMDM normalizing phenotype, gene expression profiling

    PMID:27316687

    Open questions at the time
    • Molecular target through which MMP-10 shifts M1/M2 balance not identified in this study
    • Whether catalytic activity is required for polarization effect not tested
  12. 2021 High

    Identifying proMMP-9 as a direct MMP-10 processing target in macrophages during fracture healing linked MMP-10's protease cascade function to a specific physiological tissue remodeling context.

    Evidence Mmp10−/− mice with delayed fracture cartilage resorption rescued by wild-type bone marrow transplant; gelatinase assays showing reduced MMP-9 activation

    PMID:34173256

    Open questions at the time
    • Whether MMP-10 directly cleaves proMMP-9 or acts through an intermediary not fully resolved
    • Cleavage site on proMMP-9 not mapped
  13. 2022 High

    Engineered TIMP-1 variants with MMP-3 selectivity over MMP-10, validated by crystal structures, revealed the precise interface residues governing TIMP-1/MMP-10 binding specificity.

    Evidence Directed evolution of yeast-displayed TIMP-1 with crystal structures of selective variants bound to MMP-3 and MMP-10

    PMID:35101440

    Open questions at the time
    • In vivo utility of MMP-3-selective TIMP-1 not tested
    • Whether these insights enable MMP-10-selective inhibitor design not demonstrated
  14. 2023 Medium

    Demonstrating that PPARγ directly binds the MMP-10 promoter during IL-4-driven M2 polarization and that MMP-10 activates STAT3 to amplify M2 polarization defined the signaling circuit underlying MMP-10's anti-inflammatory function in macrophages.

    Evidence ChIP for PPARγ at MMP-10 promoter, MMP10 overexpression/knockout in Kupffer cells and mice, NASH model with STAT3 pathway analysis

    PMID:37844469

    Open questions at the time
    • How a secreted protease activates intracellular STAT3 not mechanistically resolved
    • Whether this PPARγ-MMP-10-STAT3 axis operates in non-hepatic macrophages
    • Single lab
  15. 2023 Medium

    Identifying SOX9 as a direct transcriptional activator of MMP-10 through ChIP-seq and showing that the SOX9-MMP-10 axis drives fibroblast activation via Wnt/β-catenin provided a new disease-relevant transcriptional pathway.

    Evidence RNA-seq, ChIP-seq, siRNA knockdown, in vivo tracheal fibrosis model

    PMID:38993791

    Open questions at the time
    • Direct SOX9 binding site on MMP-10 promoter not individually mutated
    • Broader applicability to other fibrotic diseases not tested
    • Single lab
  16. 2024 Medium

    A missense variant (p.L245P) in MMP10 found in families with premature myocardial infarction, shown to alter the TIMP-1 binding interface and cause pro-inflammatory macrophage behavior, provided the first human genetic link between MMP-10 dysfunction and cardiovascular disease.

    Evidence Whole-exome sequencing of two families, molecular dynamics simulation, functional assays in variant-expressing THP-1 macrophages

    PMID:38806571

    Open questions at the time
    • Variant not yet validated in large cohort or animal knock-in
    • Whether catalytic activity is altered not directly measured
    • Only two families identified
  17. 2025 High

    Demonstrating that MMP-10 directly cleaves nephrin to injure podocytes established a novel substrate and pathogenic mechanism in glomerulonephritis.

    Evidence Mmp10−/− mice in anti-GBM nephritis showing protection, in vitro nephrin cleavage assay, MMP-10 overexpression/knockdown in podocytes

    PMID:40328459

    Open questions at the time
    • Nephrin cleavage site not mapped
    • Whether other slit diaphragm proteins are also MMP-10 substrates
    • Relevance to human glomerulonephritis not confirmed
  18. 2025 Medium

    Showing that endothelial TRIM35 suppresses MMP-10 transcription through K63-linked ubiquitination of RelB and noncanonical NF-κB signaling defined a new layer of MMP-10 transcriptional repression in vascular biology.

    Evidence TRIM35 conditional endothelial knockout mice with increased MMP-10 and vascular calcification, ubiquitination assays, in situ MMP-10 targeting rescue

    PMID:39865905

    Open questions at the time
    • Direct RelB binding site on MMP-10 promoter not identified
    • Single lab
    • Whether this pathway operates in non-endothelial cells unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how secreted MMP-10 activates intracellular STAT3 to drive M2 polarization; the full catalog of direct proteolytic substrates in vivo; whether catalytic activity versus non-catalytic signaling underlies macrophage polarization; and how competing transcriptional regulators are integrated in cell-type- and context-specific MMP-10 expression.
  • Mechanism linking extracellular MMP-10 to intracellular STAT3 activation unknown
  • Comprehensive in vivo degradomics not performed
  • Catalytic activity requirement for immune functions not formally tested with catalytic-dead mutant

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 6 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-168256 Immune System 3
Partners
MEF2AMMP1MMP9NEPHRINSTAT3TIMP1TIMP2

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 MMP-10 activates proMMP-1 and is activated by multiple serine proteases (plasma kallikrein, trypsin, neutrophil elastase, cathepsin G, tryptase, chymase), and MMP-10-induced activation of MMP-1 mediates capillary tube regression and collagen gel contraction in 3D collagen matrices. siRNA knockdown of MMP-10 markedly delayed capillary tube regression, while adenoviral overexpression of MMP-10 accelerated serine protease-induced regression. siRNA knockdown, recombinant adenoviral overexpression, 3D collagen matrix tube regression assay, zymography Journal of cell science High 15870107
2004 Stromelysin-2 (MMP-10) degrades laminin-5 in vitro and promotes keratinocyte migration. Transgenic mice expressing constitutively active MMP-10 in keratinocytes showed aberrant keratinocyte organization at wound sites, altered laminin-5 deposition, mislocalized β1-integrins and phospho-focal adhesion kinase, and increased keratinocyte apoptosis, indicating MMP-10 controls keratinocyte migration through limited matrix degradation. In vitro degradation assay, transgenic mouse model (constitutively active mutant), immunohistochemistry, migration assay Molecular biology of the cell High 15371548
2012 The crystal structure of TIMP-1 bound to the MMP-10 catalytic domain was solved at 1.9 Å resolution. TIMP-1 inhibits MMP-10 catalytic domain with Ki of 1.1 × 10⁻⁹ M (10-fold weaker than MMP-3); TIMP-2 inhibits with Ki of 5.8 × 10⁻⁹ M. Structural comparison revealed differences at the binding interface that explain differential inhibition of stromelysin family members by TIMPs. X-ray crystallography, enzyme kinetics (multiple kinetic approaches), equilibrium inhibition constants The Journal of biological chemistry High 22427646
2013 MMP-10 is required for macrophage migration and invasion. RNAi silencing of MMP10 in primary macrophages markedly reduced migration (reversed by exogenous active MMP-10 protein); Mmp10-/- bone marrow-derived macrophages displayed significantly reduced migration over fibronectin and impaired invasion into Matrigel supplemented with fibronectin. RNAi silencing, Mmp10-/- knockout macrophages, time-lapse microscopy, migration and invasion assays, rescue with exogenous protein PloS one High 23691065
2016 MMP-10 (stromelysin-2) moderates macrophage activation state: Mmp10-/- mice showed ~3-fold greater macrophage numbers after Pseudomonas aeruginosa infection, with elevated M1 markers and reduced M2 markers persisting longer than in wild-type. Adoptive transfer of wild-type BMDM into Mmp10-/- mice normalized infection-induced morbidity, demonstrating that MMP-10 production by macrophages is the protective mechanism. Mmp10-/- knockout mice, adoptive transfer of bone marrow-derived macrophages, global gene expression analysis, in vitro macrophage culture Journal of immunology High 27316687
2015 Macrophage MMP-10 regulates collagenolytic activity in wounds: Mmp10-/- wounds showed increased collagen deposition, skin stiffness, and reduced collagenolytic activity with decreased MMP-8 and MMP-13 (particularly MMP-13) expression. Ablation and adoptive transfer experiments demonstrated that this collagenolytic function resides in alternatively activated (M2) resident macrophages. Mmp10-/- knockout mice, cell ablation, adoptive transfer, wound mechanical testing, immunohistochemistry, cell-based models The Journal of investigative dermatology High 25927164
2012 Absence of MMP-10 exacerbates DSS-induced colitis and promotes colonic dysplasia. Bone marrow transplant experiments confirmed that bone marrow-derived MMP-10 contributes to resolution of colitis severity, placing MMP-10 in the myeloid cell compartment as required for inflammation resolution. Mmp10-/- knockout mice, DSS colitis model, bone marrow transplant, histological scoring Laboratory investigation High 23044923
2009 TGF-β transcriptionally induces MMP-10 through MEF2A activation: TGF-β promotes proteasome-dependent degradation of class IIa HDACs, leading to MEF2A acetylation and binding to the MMP-10 promoter. Knockdown of MEF2A reduced MMP-10 induction; overexpression of HDACs inhibited it; chromatin immunoprecipitation showed increased histone acetylation around the MEF2 site. Promoter-reporter assay, siRNA knockdown, ChIP, HDAC overexpression/knockdown Oncogene High 19935709
2014 MMP-10 is required for efficient skeletal muscle regeneration. Mmp10-/- muscles showed impaired endothelial cell recruitment, reduced ECM proteins, diminished collagen deposition, and decreased fiber size after notexin injury, resulting in delayed regeneration. In mdx (DMD model) mice, MMP-10 knockout worsened the dystrophic phenotype. Recombinant human MMP-10 added to injured muscles accelerated repair. MMP-10-mediated muscle repair was associated with VEGF/Akt signaling. Mmp10-/- knockout mice, notexin injury model, mdx cross, siRNA silencing in vivo, recombinant protein rescue, immunohistochemistry, signaling pathway analysis Stem cells High 24123596
2014 CXCR4/SDF1-regulated muscle repair is dependent on MMP-10 activity: SDF1 and CXCR4 are upregulated in injured muscle, and MMP-10-activity mediates the regenerative effect of this axis. AMD3100 (CXCR4 antagonist) or siRNA silencing of SDF1/CXCR4 impaired regeneration; SDF1 ligand addition accelerated repair in an MMP-10-dependent manner. siRNA silencing in vivo, pharmacological inhibition (AMD3100), recombinant SDF1, muscle injury model Stem cells and development Medium 24548137
2014 MMP-10 deficiency impairs tissue repair after hind limb ischemia, causing delayed reperfusion, increased necrosis, and increased neutrophil/macrophage infiltration. MMP-10 deficiency resulted in higher Cxcl1 mRNA and protein due to lack of transcriptional inhibition; siRNA knockdown confirmed this. Injection of MMP-10 into Mmp10-/- mice rescued the phenotype. Mmp10-/- knockout mice, PET imaging, immunohistochemistry, siRNA in vivo, recombinant protein rescue, mRNA analysis FASEB journal High 25414484
2021 MMP-10 is expressed by hematopoietic cells during fracture healing and required for cartilage resorption. Mmp10-/- mice showed delayed cartilage resorption and TRAP-positive cell accumulation at 14 days post-fracture. Wild-type bone marrow transplant rescued this phenotype. MMP-10 functions by enabling proMMP-9 processing in macrophages, as Mmp10-/- macrophages showed reduced gelatinase activity. Mmp10-/- knockout mice, bone marrow transplant rescue, gelatinase activity assay, immunohistochemistry Journal of bone and mineral research High 34173256
2005 Zinc finger protein 267 (ZNF267) acts as a negative transcriptional repressor of MMP-10 in hepatic stellate cells. ZNF267 localizes constitutively to the nucleus, represses MMP-10 gene expression (shown by microarray and RNase protection assay), and binds directly to the MMP-10 promoter as demonstrated by chromatin immunoprecipitation. ChIP, reporter gene assay, microarray, RNase protection assay, fluorescence localization Biochemical and biophysical research communications High 16054593
2011 CRP promotes MMP-10 expression and activity in cardiomyocytes via c-Raf/MEK/ERK and JAK1/ERK signaling pathways. Blockade of ERK1/2 (U0126) or JAK1 (piceatannol) significantly decreased CRP-induced MMP-10 expression. DNA binding sites for AP-1 and STAT3 in cardiomyocyte nuclei mediate CRP-induced MMP-10 expression. Western blot, real-time PCR, casein zymography, pharmacological inhibitors, transcription factor binding analysis Cellular signalling Medium 22142512
2010 MMP-10 is induced by VEGF in endothelial cells via Ets-1 transcription factor (but not ERP/NET/ELK3), through PI3K and MAPK pathways. MMP-10 siRNA inhibited VEGF-induced endothelial cell migration and tube formation in vitro, and vessel formation in Matrigel plugs in vivo, demonstrating a functional role in VEGF-induced angiogenesis. Quantitative RT-PCR, siRNA knockdown, migration assay, tube formation assay, in vivo Matrigel plug assay, pharmacological inhibitors Journal of cellular physiology High 20432469
2011 β1 integrin signaling via the ERK/MAPK pathway increases MMP-10 mRNA and protein expression in human lymphatic endothelial cells undergoing tubulogenesis, and MMP-10 knockdown impairs lymphatic endothelial cell tubulogenesis in collagen I matrices. siRNA knockdown, protein screening, ERK/MAPK pathway inhibition, tubulogenesis assay Matrix biology Medium 21406228
2011 The transcription factor CHF1/Hey2 represses MMP-10 expression through multiple E-boxes in the MMP-10 promoter. Loss or knockdown of CHF1/Hey2 in vascular smooth muscle cells leads to increased MMP-10 expression and activity at baseline. Mutation of E-boxes abolished CHF1/Hey2 repression and diminished constitutive expression. Promoter-reporter assay, E-box mutagenesis, siRNA knockdown, CHF1/Hey2 knockout cells Biochemical and biophysical research communications Medium 22079635
2020 Recombinant human MMP-10 induces overexpression of inflammatory, fibrotic, and osteogenic markers (IL-1β, α-SMA, vimentin, collagen, BMP-4, Sox9, OPN, BMP-9, Smad 1/5/8) and cell mineralization in aortic valve interstitial cells through a mechanism involving Akt phosphorylation. These effects were prevented by TIMP-1 or an anti-MMP-10 antibody. Recombinant protein treatment, antibody neutralization, TIMP-1 inhibition, western blot, mineralization assay Arteriosclerosis, thrombosis, and vascular biology Medium 32188274
2017 MMP-10 provides neuroprotection and enhances thrombolysis in experimental ischemic stroke: MMP-10 reduced tPA-promoted endothelial ionic permeability, preserved claudin-5 expression, decreased ERK1/2 activation, and prevented tPA-mediated neuronal excitotoxicity and calcium influx in vitro. These effects were reversed by blocking MMP-10 activity with a monoclonal antibody. In vitro endothelial and neuronal cell culture, permeability assay, western blot, calcium imaging, antibody neutralization, in vivo stroke model Cardiovascular research Medium 28379489
2018 MMP-10 treatment was more effective than tPA at reducing infarct size and neurodegeneration in a diabetic mouse model of ischemic stroke. MMP-10 reduced oxidative stress and blood-brain barrier permeability without increasing brain bleeding. TAT complex levels were reduced by MMP-10 treatment. Streptozotocin-induced diabetic mouse model, intraluminal thrombin stroke model, infarct measurement, immunohistochemistry, ELISA Translational stroke research Medium 30051168
2018 Combined sustained release of BMP-2 and MMP-10 from PLGA microspheres significantly enhanced BMP-2-mediated osteogenesis in calvarial critical-size defects in mice, increasing bone fill percentage and mineral apposition rate compared to BMP-2 alone. In vivo calvarial defect model, PLGA microsphere delivery, histology, fluorescent double-labeling Drug delivery Medium 29516759
2023 MMP-10 alleviates non-alcoholic steatohepatitis by promoting macrophage M2 polarization. PPARγ binds to the MMP-10 promoter and upregulates MMP-10 expression when IL-4 stimulates M2 polarization. MMP-10 then activates the downstream STAT3 signaling pathway to further induce M2 polarization, reducing IL-1β and TNF-α while increasing IL-10. MMP10 overexpression/knockout Kupffer cells and mice, ChIP (PPARγ-MMP10 promoter binding), HFD NASH model, STAT3 pathway analysis International immunopharmacology Medium 37844469
2018 Macrophage MMP-10 mediates immune tolerance to TLR7 ligand (imiquimod): second exposure to IMQ in Mmp10-/- mice produced the same pro-inflammatory response as first exposure, whereas wildtype mice showed markedly abrogated response. Mmp10-/- macrophages in vitro failed to become refractory after prior IMQ exposure. Tolerance was associated with upregulation of TNFAIP3, IRAK3, IL-10, and TGFβ1 in wildtype but not Mmp10-/- mice. Mmp10-/- knockout mice, in vivo TLR7 tolerance model, bone marrow-derived macrophage cultures, cytokine/gene expression analysis Frontiers in immunology Medium 30564235
2022 MMP-3-selective TIMP-1 variants were engineered via directed evolution of yeast-displayed TIMP-1. Crystal structures of MMP-3-selective TIMP-1 variants bound to MMP-3 and MMP-10 showed how structural alterations in the N-terminal and C-terminal TIMP-1 domains create selective interactions with MMP-3 and disrupt interactions with MMP-10, providing mechanistic insight into TIMP-1/MMP-10 binding specificity. Directed evolution (yeast display), protein crystallography, counter-selective screening The Journal of biological chemistry High 35101440
2025 MMP-10 aggravates podocyte injury in glomerulonephritis: MMP-10 knockout mice showed less albuminuria and reduced pro-inflammatory/pro-fibrotic gene expression in anti-GBM nephritis. In vitro, MMP-10 overexpression upregulated TNF-α-induced inflammation in podocytes; MMP-10 knockdown mitigated it. Activated MMP-10 cleaved nephrin in vitro, directly contributing to podocyte injury. Mmp10-/- knockout mice, anti-GBM nephritis model, MMP-10 overexpression/knockdown in podocytes, in vitro nephrin cleavage assay, co-culture Nephrology, dialysis, transplantation High 40328459
2025 Endothelial TRIM35 inhibits MMP-10 expression and secretion by promoting K63-linked ubiquitination of RelB, maintaining its nuclear localization and suppressing MMP-10 nuclear transcription through the noncanonical NF-κB signaling pathway. TRIM35 conditional endothelial knockout mice showed increased MMP-10 secretion and severe SMC calcification in artery grafts, which was rescued by targeting MMP-10 in situ. TRIM35 conditional endothelial KO mice, in vitro co-culture, ubiquitination assay, nuclear localization analysis, in situ MMP-10 targeting, single-cell analysis Advanced science Medium 39865905
2024 NOX5-generated ROS upregulate MMP-10 expression in endothelial cells through the redox-sensitive JNK/AP-1 signaling pathway, promoting cell migration. NOX5 and MMP-10 silencing prevented the pro-migratory effect. This was enhanced by angiotensin II. MMP-10 protein was increased in hearts of NOX5-expressing mice. NOX5 overexpression model, siRNA silencing, wound healing migration assay, promoter activity measurement, JNK/AP-1 pathway inhibition, in vivo NOX5-expressing mouse model Antioxidants Medium 39456453
2014 YY1 suppresses MMP-10 expression and invasion of pancreatic cancer cells through a MUC4/ErbB2/p38/MEF2C-dependent mechanism. YY1 knockdown enhanced invasion; YY1 overexpression suppressed it both in vitro and in vivo. Signal transduction pathway blockage experiments and luciferase assays confirmed the downstream pathway linking YY1 to MMP-10 transcriptional regulation. siRNA knockdown, overexpression, luciferase reporter assay, signal transduction blockade, xenograft models, DGE sequencing Molecular cancer Medium 24884523
2023 miR-944 negatively regulates MMP10 by targeting its 3'-UTR. MMP10 knockdown suppressed proliferation, migration, and invasion of tongue cancer cells. MMP10 overexpression promoted nodal and distant metastasis in vivo and upregulated AXL through epithelial-mesenchymal transition; AXL expression was essential and sufficient to mediate MMP10 overexpression functional consequences. 3'-UTR luciferase reporter assay, siRNA knockdown, overexpression, orthotopic tongue cancer mouse model, in vivo metastasis assay Communications biology High 36650344
2009 IL-6 regulates MMP-10 expression via the JAK2/STAT3 pathway in lung adenocarcinoma cells: IL-6 moderately reduces MMP-10 mRNA while strongly enhancing MMP-10 protein mass. AG490 (JAK2 inhibitor) blocked both IL-6-induced STAT3 upregulation and the divergent effects on MMP-10 mRNA and protein. Pharmacological inhibition (AG490), real-time RT-PCR, western blot Anticancer research Low 20032397
2024 A missense variant p.L245P in MMP10 found in two families with premature myocardial infarction alters the MMP10-TIMP1 binding interface (reduced binding energy, altered protein surface, minimized substrate-binding cleft volume by molecular dynamics simulation) and causes macrophages to be more adherent, less migratory, and to secrete higher levels of CXCL1 and CXCL8 pro-inflammatory chemokines. Whole-exome sequencing, molecular dynamics simulation, THP-1 cell transfection, macrophage adhesion and migration assays, chemokine ELISA Scientific reports Medium 38806571
1997 Murine stromelysin-2 (MMP-10) is secreted and can undergo autocatalytic processing activated by the organomercurial salt APMA, consistent with the prodomain autoinhibitory mechanism shared by MMPs. COS cell expression of recombinant protein, APMA activation assay Gene Medium 9427548
2020 Ski protein associates with pericentromeric chromatin during mitosis and is required for H3K9 tri-methylation at major satellite repeats and for repression of Mmp10 (and Mmp3, Mmp13) genes located near pericentromeric DNA. ChIP assays confirmed Ski binding to the Mmp10 promoter and increased H3K9me3 levels there; Ski-/- MEFs showed augmented MMP activity. ChIP, H3K9 methylation analysis, fluorescence localization, Ski-/- MEFs, MMP activity assay Journal of molecular biology Medium 32198114
2023 SOX9 directly targets MMP10 (identified by RNA-seq and ChIP-seq), promoting MMP10 expression through the Wnt/β-catenin signaling pathway. MMP10 in turn promotes ECM degradation. SOX9 knockdown in vivo ameliorated tracheal fibrosis, and the SOX9-MMP10-ECM axis was identified as central to fibroblast activation in tracheal injury. RNA-seq, ChIP-seq, siRNA knockdown, adenoviral overexpression, in vivo tracheal fibrosis model Genes & diseases Medium 38993791
2025 MMP-10 induces Ca²⁺ mobilization in dorsal root ganglion neurons through a PAR1-independent mechanism, distinguishing it from MMP3, MMP8, and MMP9 which act through PAR1/PLC. Pre-treatment with MMP-10 did not reduce neuronal response to PAR1 agonist, unlike MMP2 and MMP13. Intracellular Ca²⁺ imaging in DRG neurons, PAR1 receptor pharmacology, PLC pathway analysis bioRxivpreprint Low
2022 MMP-10 deficiency in hypertrophic chondrocytes decreases expression of Col II, Col X, Runx2, and MMP-13, and increases chondrocyte apoptosis, impairing endochondral osteogenesis. This was observed in both Kashin-Beck disease patient cartilage and in in vitro ATDC5 cell models with MMP-10 shRNA knockdown. shRNA knockdown in ATDC5 cells, flow cytometry (apoptosis), RT-PCR, Western blot, immunohistochemistry Cartilage Medium 35818290

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10. Annals of the rheumatic diseases 195 12379519
2005 MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. Journal of cell science 163 15870107
2004 Activities of the matrix metalloproteinase stromelysin-2 (MMP-10) in matrix degradation and keratinocyte organization in wounded skin. Molecular biology of the cell 108 15371548
2014 Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. Molecular cancer 102 24884523
2012 Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure. The Journal of biological chemistry 93 22427646
1998 Stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) expression in developing human bone: potential roles in skeletal development. Bone 92 9662124
2009 Vascular MMP-9/TIMP-2 and neuronal MMP-10 up-regulation in human brain after stroke: a combined laser microdissection and protein array study. Journal of proteome research 89 19317417
2013 Macrophage migration and invasion is regulated by MMP10 expression. PloS one 79 23691065
2004 Collagenase-1 (MMP-1), matrilysin-1 (MMP-7), and stromelysin-2 (MMP-10) are expressed by migrating enterocytes during intestinal wound healing. Scandinavian journal of gastroenterology 78 15545168
2003 Human diabetic corneas preserve wound healing, basement membrane, integrin and MMP-10 differences from normal corneas in organ culture. Experimental eye research 77 12873452
2008 Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli. Frontiers in bioscience : a journal and virtual library 76 17981764
2016 Stromelysin-2 (MMP10) Moderates Inflammation by Controlling Macrophage Activation. Journal of immunology (Baltimore, Md. : 1950) 75 27316687
2015 MMP-10 Regulates Collagenolytic Activity of Alternatively Activated Resident Macrophages. The Journal of investigative dermatology 72 25927164
2001 Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers. British journal of cancer 71 11237387
2010 Expression profiling of ETS and MMP factors in VEGF-activated endothelial cells: role of MMP-10 in VEGF-induced angiogenesis. Journal of cellular physiology 65 20432469
2009 Matrix metalloproteinases (MMP) 1 and MMP10 but not MMP12 are potential oral cancer markers. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 65 19489686
2012 Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia. Laboratory investigation; a journal of technical methods and pathology 63 23044923
2003 Expression of MMP-2, MMP-7, MMP-9, MMP-10 and MMP-11 in human astrocytic and oligodendroglial gliomas. Anticancer research 62 14666700
2004 MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas. Neoplasia (New York, N.Y.) 56 15720804
2020 A Role for MMP-10 (Matrix Metalloproteinase-10) in Calcific Aortic Valve Stenosis. Arteriosclerosis, thrombosis, and vascular biology 51 32188274
2013 Enhanced wound healing, kinase and stem cell marker expression in diabetic organ-cultured human corneas upon MMP-10 and cathepsin F gene silencing. Investigative ophthalmology & visual science 44 24255036
2014 MMP-10 is required for efficient muscle regeneration in mouse models of injury and muscular dystrophy. Stem cells (Dayton, Ohio) 41 24123596
2009 Transcriptional induction of MMP-10 by TGF-beta, mediated by activation of MEF2A and downregulation of class IIa HDACs. Oncogene 41 19935709
2010 Age- and gender-dependent changes in connective tissue remodeling: physiological differences in circulating MMP-3, MMP-10, TIMP-1 and TIMP-2 level. Gerontology 39 20215736
2019 Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET. Allergy 38 30667542
2009 IL-6 regulates MMP-10 expression via JAK2/STAT3 signaling pathway in a human lung adenocarcinoma cell line. Anticancer research 38 20032397
2019 Methanogenesis marker protein 10 (Mmp10) from Methanosarcina acetivorans is a radical S-adenosylmethionine methylase that unexpectedly requires cobalamin. The Journal of biological chemistry 36 31113866
2008 Selective iNOS inhibitor 1400W enhances anti-catabolic IL-10 and reduces destructive MMP-10 in OA cartilage. Survey of the effects of 1400W on inflammatory mediators produced by OA cartilage as detected by protein antibody array. Clinical and experimental rheumatology 36 18565249
2016 AJUBA promotes the migration and invasion of esophageal squamous cell carcinoma cells through upregulation of MMP10 and MMP13 expression. Oncotarget 35 27172796
2014 The CXCR4/SDF1 axis improves muscle regeneration through MMP-10 activity. Stem cells and development 35 24548137
2012 The immunohistochemical characterization of MMP-2, MMP-10, TIMP-1, TIMP-2, and podoplanin in oral squamous cell carcinoma. Oral surgery, oral medicine, oral pathology and oral radiology 34 22769410
2007 Expression of MMP-9, MMP-10 and TNF-alpha and lack of epithelial MMP-1 and MMP-26 characterize pyoderma gangrenosum. Journal of cutaneous pathology 34 18001410
2022 MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension. International journal of biological sciences 33 34975336
2020 Palmatine ameliorates Helicobacter pylori-induced chronic atrophic gastritis by inhibiting MMP-10 through ADAM17/EGFR. European journal of pharmacology 32 32569674
2013 Activation of the PKC pathway stimulates ovarian cancer cell proliferation, migration, and expression of MMP7 and MMP10. Biology of reproduction 31 23843242
2017 Genomic characterization of tobacco/nut chewing HPV-negative early stage tongue tumors identify MMP10 asa candidate to predict metastases. Oral oncology 30 28939077
2004 Induction of MMP-10 and MMP-1 in a squamous cell carcinoma cell line by ultraviolet radiation. Biological chemistry 30 14977049
2018 Combined sustained release of BMP2 and MMP10 accelerates bone formation and mineralization of calvaria critical size defect in mice. Drug delivery 28 29516759
2020 MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade. Scientific reports 26 31913319
2022 Elevated MMP10/13 mediated barrier disruption and NF-κB activation aggravate colitis and colon tumorigenesis in both individual or full miR-148/152 family knockout mice. Cancer letters 25 34979166
2014 Functional MMP-10 is required for efficient tissue repair after experimental hind limb ischemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 25414484
2022 Engineering of tissue inhibitor of metalloproteinases TIMP-1 for fine discrimination between closely related stromelysins MMP-3 and MMP-10. The Journal of biological chemistry 24 35101440
2018 MMP10 Promotes Efficient Thrombolysis After Ischemic Stroke in Mice with Induced Diabetes. Translational stroke research 23 30051168
2020 Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross-sectional study. Scandinavian journal of immunology 20 32853407
2020 Gentiopicroside ameliorates ethanol-induced gastritis via regulating MMP-10 and pERK1/2 signaling. International immunopharmacology 20 33296781
2019 Elevated expression of cellular SYNE1, MMP10, and GTPase1 and their regulatory role in hepatocellular carcinoma progression. Protoplasma 19 31428857
2017 MMP-10, MMP-7, TIMP-1 and TIMP-2 mRNA expression in esophageal cancer. Acta biochimica Polonica 19 28510611
2011 Type-specific dysregulation of matrix metalloproteinases and their tissue inhibitors in end-stage heart failure patients: relationship between MMP-10 and LV remodelling. Journal of cellular and molecular medicine 19 20219015
2009 MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer. Experimental dermatology 19 19601983
2023 Role of miR-944/MMP10/AXL- axis in lymph node metastasis in tongue cancer. Communications biology 18 36650344
2009 Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma. Virchows Archiv : an international journal of pathology 18 19921252
2005 Zinc finger protein 267 is up-regulated during the activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10. Biochemical and biophysical research communications 18 16054593
1997 cDNA cloning and expression of the gene encoding murine stromelysin-2 (MMP-10). Gene 18 9427548
2011 CRP promotes MMP-10 expression via c-Raf/MEK/ERK and JAK1/ERK pathways in cardiomyocytes. Cellular signalling 17 22142512
2007 Expression of MMP-10 in lung cancer. Anticancer research 17 17695449
2023 MMP10 alleviates non-alcoholic steatohepatitis by regulating macrophage M2 polarization. International immunopharmacology 16 37844469
2009 Stromelysin-2 (MMP-10) deficiency does not affect adipose tissue formation in a mouse model of nutritionally induced obesity. Biochemical and biophysical research communications 16 19732744
2019 MMP2 and MMP10 Polymorphisms Are Related to Steroid-Induced Osteonecrosis of the Femoral Head among Chinese Han Population. BioMed research international 15 31192258
2017 New thrombolytic strategy providing neuroprotection in experimental ischemic stroke: MMP10 alone or in combination with tissue-type plasminogen activator. Cardiovascular research 15 28379489
2017 Genetic Association of MMP10, MMP14, and MMP16 with Dental Caries. International journal of dentistry 14 28348596
2019 Novel specific human and mouse stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) antibodies for biochemical and immunohistochemical analyses. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 13 30761682
2020 Matrix Metalloproteinase Genes (MMP1, MMP10, MMP12) on Chromosome 11q22 and the Risk of Non-Contact Anterior Cruciate Ligament Ruptures. Genes 11 32650441
2017 Characterization of the early molecular changes in the glomeruli of Cd151 -/- mice highlights induction of mindin and MMP-10. Scientific reports 11 29167507
2022 MMP-10 Deficiency Effects Differentiation and Death of Chondrocytes Associated with Endochondral Osteogenesis in an Endemic Osteoarthritis. Cartilage 9 35818290
2021 miR-496/MMP10 Is Involved in the Proliferation of IL-1β-Induced Fibroblast-Like Synoviocytes Via Mediating the NF-κB Signaling Pathway. Inflammation 9 33548006
2021 Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 9 34173256
2018 Macrophage MMP10 Regulates TLR7-Mediated Tolerance. Frontiers in immunology 9 30564235
2009 Aldose reductase inhibitor counteracts the attenuated adhesion of human corneal epithelial cells induced by high glucose through modulation of MMP-10 expression. Diabetes research and clinical practice 9 19682763
2021 Enhanced Expression but Decreased Specific Activity of Matrix Metalloproteinase 10 (MMP-10) in Comparison with Matrix Metalloproteinase 3 (MMP-3) in Human Urinary Bladder Carcinoma. Journal of clinical medicine 8 34441979
2016 Differential immunohistochemical expression of matrix metalloproteinase-10 (MMP-10) in non-melanoma skin cancers of the head and neck. Pathology, research and practice 8 27567711
2021 The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status. Pharmaceutics 7 34209593
2022 Elevated expression of ISY1, APOA-1, SYNE1, MTG1, and MMP10 at HCC initiation: HCC specific protein network involving interactions of key regulators of lipid metabolism, EGFR signaling, MAPK, and splicing pathways. Protoplasma 6 35962262
2022 Association between Circulating Levels of 25-Hydroxyvitamin D3 and Matrix Metalloproteinase-10 (MMP-10) in Patients with Type 2 Diabetes. Nutrients 6 36079742
2017 Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes. International journal of nanomedicine 6 28223796
2011 β1 integrin regulates MMP-10 dependant tubulogenesis in human lymphatic endothelial cells. Matrix biology : journal of the International Society for Matrix Biology 6 21406228
2024 Hepatocyte growth factor upregulates MMP1 and MMP10 expression and resolves corneal fibrosis. Scientific reports 5 39488561
2023 Radiosensitivity in Non-Small-Cell Lung Cancer by MMP10 through the DNA Damage Repair Pathway. Journal of oncology 5 36908704
2019 MMP-10 and TIMP-1 as indicators of severe sepsis in adult hematological patients with febrile neutropenia. Leukemia & lymphoma 5 31122146
2011 Regulation of MMP10 expression by the transcription factor CHF1/Hey2 is mediated by multiple E boxes. Biochemical and biophysical research communications 5 22079635
2022 Computational study revealed a "pull-push" radical transfer mechanism of Mmp10-catalyzed C-methylation of arginine. Chemical communications (Cambridge, England) 4 35666280
2011 Evaluation of MMP-1, MMP-10, TIMP-1, a-SMA and TGF-b1 in angiofibromas of tuberous sclerosis. Minerva stomatologica 4 21252847
2024 NADPH Oxidase 5 (NOX5) Upregulates MMP-10 Production and Cell Migration in Human Endothelial Cells. Antioxidants (Basel, Switzerland) 3 39456453
2023 Role of MMP1 and MMP10 in local invasion and distant metastasis in different levels of oral squamous cell carcinoma - A immunohistochemical comparative study. Journal of oral and maxillofacial pathology : JOMFP 3 37854907
2020 Ski Is Required for Tri-Methylation of H3K9 in Major Satellite and for Repression of Pericentromeric Genes: Mmp3, Mmp10 and Mmp13, in Mouse Fibroblasts. Journal of molecular biology 3 32198114
2023 Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair. Genes & diseases 2 38993791
2022 Higher Content but Not Activity of Stromelysin-2 (MMP-10) in Comparison to Stromelysin-1 (MMP-3) in Human Renal Carcinoma. International journal of environmental research and public health 2 36231910
2021 MMP-10 rs17435959 Polymorphism is Associated with the Formation and Stability of Carotid Atherosclerosis Plaque: A Case-Control Study. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2 34418671
2009 Molecular characterization, mapping, and haplotype analysis of porcine matrix metalloproteinase genes MMP1 and MMP10. Biochemical genetics 2 19639408
2025 Endothelial TRIM35-Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 39865905
2026 Targeting PLK1 Reduces MMP10 to Enhance Radiosensitivity in HPV- Head and Neck Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 0 41252565
2026 Analysis of paired primary-metastatic renal cancer lesions reveals RCN3-MMP10 axis facilitates lung metastasis. Cellular signalling 0 41966439
2025 Metformin Inhibits the Development of Helicobacter pylori-Associated Gastritis by Regulating the ERK-MMP10-IL-1β Axis. Cell biochemistry and biophysics 0 40180700
2025 Matrix metalloproteinase (MMP)-10 aggravates podocyte injury in glomerulonephritis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 0 40328459
2025 Role of Matrilysins (MMP-7, MMP-26) and Stromelysins (MMP-3, MMP-10) in Diagnosing Cervical Cancer Patients. Biomedicines 0 41462922
2024 Identification of a functional missense variant in the matrix metallopeptidase 10 (MMP10) gene in two families with premature myocardial infarction. Scientific reports 0 38806571