Affinage

NOX4

NADPH oxidase 4 · UniProt Q9NPH5

Length
578 aa
Mass
66.9 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOX4 is a constitutively active, NADPH-dependent oxidase homologous to the phagocyte catalytic subunit gp91phox that generates reactive oxygen species to drive spatially confined redox signaling (PMID:11376945, PMID:19061439). Distinct structural elements set its output and address: the cytosolic tail confers subunit-independent constitutive activity while the N-terminal region directs ER localization and dictates that NOX4 releases H2O2 rather than superoxide (PMID:19061439), a determinant confirmed by genetic models showing NOX4 produces H2O2 constitutively (PMID:26385958). It localizes to the endoplasmic reticulum, mitochondria, and ER-mitochondria contact sites (MAMs) and requires p22phox as a cofactor, with the partner interaction demonstrated directly in endothelial cells (PMID:15706079, PMID:19706525, PMID:16987004); at mitochondrial membranes, CYB5R3 directly interacts with NOX4 and, through coenzyme Q, is required for optimal H2O2 output (PMID:34656824). NOX4 activity is allosterically inhibited by direct ATP binding (PMID:29051480) and negatively regulated by FYN-mediated phosphorylation at Y566 (PMID:27525436). The H2O2 it produces acts on defined targets to control discrete cellular programs: it binds the PP1-targeting subunit GADD34 at the ER and oxidizes the PP1 metal center to sustain eIF2α phosphorylation and ATF4-driven autophagy (PMID:26742780, PMID:24492492), oxidizes HDAC4 to disrupt the HDAC4/Mef2A complex and enable endothelial tube formation (PMID:32818796), oxidizes AKT to retain PP2A in the cytosol and preserve γH2AX-dependent DNA damage surveillance (PMID:33836590), activates Nrf2-dependent antioxidant programs (PMID:21554947), and at the MAM augments Akt-dependent InsP3R phosphorylation to restrict ER-to-mitochondria Ca2+ flux and limit mitochondrial permeability transition (PMID:33001475). Through these outputs NOX4 governs proliferation, angiogenesis, metabolic gene expression, and cell-fate decisions including ferroptosis, and its transcription is controlled by inputs including STAT5, HOXD10, ATF3, and IRP1 binding to IRE-like promoter sequences (PMID:26308771, PMID:38844470, PMID:38993139, PMID:36738798). NOX4-derived signaling is implicated across diabetic kidney disease, cardiac remodeling, leukemic transformation, tauopathy, and cancer (PMID:16135519, PMID:27525436, PMID:26308771, PMID:34922273).

Mechanistic history

Synthesis pass · year-by-year structured walk · 29 steps
  1. 2001 Medium

    Establishing NOX4 as an NADPH oxidase family member answered whether it could be an enzymatic ROS source by showing it shares the catalytic architecture of gp91phox.

    Evidence cDNA cloning and sequence/domain analysis with tissue expression profiling

    PMID:11376945

    Open questions at the time
    • Enzymatic activity not directly reconstituted in this work
    • ROS species (H2O2 vs O2-) not determined
    • Subcellular site not defined
  2. 2003 Medium

    Linking NOX4 to angiotensin II-induced ROS and Akt activation placed it in a defined receptor-driven signaling pathway in mesangial cells.

    Evidence Antisense knockdown, dominant-negative Rac1, ROS and Akt phosphorylation assays

    PMID:12842860

    Open questions at the time
    • Antisense specificity limits, no genetic KO
    • Direct ROS species not resolved
    • Mechanism of Rac1/arachidonate input unclear
  3. 2005 Medium

    ER localization of NOX4 answered where the enzyme acts, distinguishing it from plasma-membrane oxidases.

    Evidence Confocal microscopy of NOX4-GFP with ER, lysosome, and mitochondrial markers in HUVECs

    PMID:15706079

    Open questions at the time
    • Based on overexpressed GFP fusion
    • Does not address mitochondrial pools reported later
    • No structural basis for targeting
  4. 2006 Medium

    Demonstrating a direct NOX4-p22phox interaction at the ER identified the obligatory cofactor needed for endothelial ROS production.

    Evidence Bimolecular fluorescence complementation, calreticulin co-localization, siRNA, ROS assays

    PMID:16987004

    Open questions at the time
    • BiFC can trap transient interactions
    • Stoichiometry not defined
    • Single lab
  5. 2009 High

    Domain-swap mapping established that the N-terminus dictates ER localization and the cytosolic tail confers constitutive, subunit-independent activity and H2O2 output, defining the structural logic of NOX4 specificity.

    Evidence Chimeric Nox1/Nox4 constructs, TIRF microscopy, ROS-type measurement in HEK293

    PMID:19061439

    Open questions at the time
    • No atomic structure
    • Mechanism of H2O2 vs O2- determination at the catalytic core unresolved
  6. 2009 Medium

    Detection of NOX4 in mitochondria broadened its localization beyond the ER and tied it to glucose-induced mitochondrial superoxide in diabetic kidney.

    Evidence Subcellular fractionation, Mitotracker confocal, MitoProt prediction, siRNA, organelle NADPH oxidase assays

    PMID:19706525

    Open questions at the time
    • Reconciliation with H2O2-only model not addressed here
    • Import/targeting mechanism unknown
  7. 2011 Medium

    Showing NOX4-derived ROS activates Nrf2 reframed NOX4 as a driver of antioxidant defense rather than purely oxidative damage.

    Evidence Transgenic cardiomyocyte overexpression, transcriptomics, glutathione assays, Nrf2-null epistasis

    PMID:21554947

    Open questions at the time
    • Overexpression context
    • Direct sensor of NOX4 H2O2 in Keap1/Nrf2 axis not identified
  8. 2015 High

    Identifying STAT5-driven NOX4 transcription and NOX4-mediated DEP-1/PTPRJ inactivation explained how NOX4 sustains oncogenic FLT3ITD signaling in leukemia.

    Evidence STAT5 ChIP on NOX4 promoter, PTP activity assay, knockout transformation assays, in vivo disease models

    PMID:26308771

    Open questions at the time
    • Site of redox-DEP1 encounter not localized
    • Generalizability beyond FLT3ITD leukemia
  9. 2016 High

    The GADD34/PP1 work provided a direct molecular target, showing NOX4 H2O2 oxidizes the PP1 metal center to sustain eIF2α phosphorylation in a spatially confined manner at the ER.

    Evidence Co-IP with GADD34, PP1 activity assays distinguishing metal-center vs thiol oxidation, in vivo ischemia and AKI models

    PMID:26742780

    Open questions at the time
    • How H2O2 is delivered to confined PP1 pool not fully resolved
    • Other PP1 holoenzymes spared but mechanism of selectivity incomplete
  10. 2016 High

    Identification of FYN-mediated Y566 phosphorylation defined a negative post-translational regulatory input restraining NOX4 in the heart.

    Evidence Co-IP, Y566 site-directed mutagenesis, activity assays, Nox4-/- rescue of FYN-/- cardiac phenotype

    PMID:27525436

    Open questions at the time
    • Structural effect of Y566 phosphorylation on catalysis unknown
    • Upstream control of FYN-NOX4 axis
  11. 2017 High

    Discovery of an ATP-binding motif established direct allosteric inhibition of NOX4 by ATP, providing a metabolic switch coupling energy state to oxidase activity.

    Evidence ATP-binding and titration activity assays, inner mitochondrial membrane fractionation, PKM2 downstream pathway, xenografts

    PMID:29051480

    Open questions at the time
    • ATP-binding site not structurally resolved
    • Inner-membrane localization claim contrasts with ER/MAM models
  12. 2017 High

    The Nox4/Nox2/p66Shc feed-forward axis showed how NOX4 H2O2 amplifies mitochondrial ROS and VEGFR2 signaling to drive angiogenesis.

    Evidence Organelle-targeted RoGFP imaging, double knockdown, p66Shc(S36A) mutant, EC migration/proliferation assays

    PMID:28424170

    Open questions at the time
    • Direct molecular link from NOX4 H2O2 to Nox2 activation not defined
    • Spatial coupling of the two oxidases unresolved
  13. 2018 High

    NOX4 H2O2 activation of TRPC6-dependent calcium influx connected the oxidase to podocyte calcium dysregulation in diabetic kidney disease.

    Evidence Nox4 KO rat, TRPC6 KO, H2O2 stimulation, calcium imaging, patch-clamp, EM

    PMID:29793963

    Open questions at the time
    • Direct oxidative modification of TRPC6 not demonstrated
    • Cell-type generality unclear
  14. 2019 Medium

    Direct CD44-NOX4 association linked HA/CD44 signaling to NOX4-driven Ca2+-handling abnormalities in atrial fibrillation.

    Evidence Co-IP, CD44-/- mice, blocking antibody, Ca2+ spark measurement, AF patient tissue

    PMID:31419440

    Open questions at the time
    • Single Co-IP without reciprocal structural mapping
    • Whether CD44 regulates NOX4 activity or only expression unclear
  15. 2020 High

    Localizing NOX4 to MAMs and showing it augments Akt-dependent InsP3R phosphorylation defined a cytoprotective role restricting ER-to-mitochondria Ca2+ flux and limiting permeability transition.

    Evidence MAM fractionation, overexpression/KO, InsP3R phosphorylation, mitochondrial Ca2+ and mPT assays, cardiac ischemia-reperfusion

    PMID:33001475

    Open questions at the time
    • How NOX4 H2O2 promotes Akt activity at MAM not fully resolved
    • Direct InsP3R oxidation not shown
  16. 2020 Medium

    ER-confined NOX4 activation of the PERK-eIF2α-ATF4 pathway during energy stress established NOX4 as an inducer of adaptive autophagy.

    Evidence Organelle-resolved NOX4 activity, genetic deletion, UPR pathway immunoblotting, autophagy flux in cardiomyocytes

    PMID:24492492

    Open questions at the time
    • Direct PERK oxidation/sensor not identified
    • Relationship to the GADD34/PP1 mechanism not integrated
  17. 2020 Medium

    Cell-type-specific KO showed endothelial NOX4-derived H2O2 mediates endothelium-to-muscle cross-talk required for exercise-induced metabolic gene expression.

    Evidence Global and endothelial-specific Nox4 KO, 14C substrate oxidation, qPCR, catalase transgenics

    PMID:33400973

    Open questions at the time
    • Identity of the cross-talk signal beyond H2O2 unknown
    • Direct muscle target genes' redox sensors undefined
  18. 2020 Medium

    Placing NOX4 downstream of SIRT1/NF-κB/FOXO defined it as an effector in tumor-induced muscle wasting.

    Evidence RNA-seq, muscle-specific Nox4 KO, pharmacological inhibition, SIRT1 reconstitution, cachexia models

    PMID:32441762

    Open questions at the time
    • Downstream NOX4 targets in wasting muscle not identified
    • Direct FOXO-NOX4 promoter binding not shown here
  19. 2020 High

    Showing NOX4 oxidizes HDAC4 to disrupt the HDAC4/Mef2A complex provided a direct chromatin-linked substrate enabling endothelial tube formation.

    Evidence Inducible overexpression, HDAC4 oxidation assay, HDAC4/Mef2A Co-IP, redox-dead NOX4 and redox-insensitive HDAC4 mutants, tube formation

    PMID:32818796

    Open questions at the time
    • Spatial route of H2O2 to nuclear/cytosolic HDAC4 unclear
    • Overexpression-based system
  20. 2010 Medium

    NOX4 was shown to promote cell cycle entry by suppressing a p53/p21 checkpoint downstream of PDGF.

    Evidence siRNA, Rb phosphorylation, cyclin D1/p53/p21 immunoblotting, co-knockdown epistasis in fibroblasts

    PMID:20531308

    Open questions at the time
    • Direct redox target upstream of p53/p21 not identified
    • Single cell type
  21. 2014 Medium

    NOX4-derived ROS was found necessary for HIF2α nuclear accumulation and tumorigenesis in VHL-deficient renal carcinoma.

    Evidence siRNA, ROS scavengers, MnSOD/catalase, nuclear fractionation, invasion/colony assays, xenografts

    PMID:24755467

    Open questions at the time
    • Molecular target linking NOX4 ROS to HIF2α transport not defined
    • Single tumor model
  22. 2021 High

    NOX4 oxidation of AKT to retain PP2A in the cytosol revealed a tumor-suppressive role maintaining γH2AX-dependent DNA damage surveillance.

    Evidence Nox4 KO mice, carcinogen models, AKT oxidation assay, PP2A fractionation, γH2AX readouts

    PMID:33836590

    Open questions at the time
    • Site of AKT oxidation and its kinetics not fully mapped
    • How redox state directs PP2A shuttling mechanistically
  23. 2021 High

    Identifying CYB5R3 as a direct NOX4 partner at the mitochondrial outer membrane defined a CoQ-dependent requirement for full H2O2 output.

    Evidence APEX2-EM, proximity biotinylation, PLA, Co-IP, CYB5R3 activity mutants, COQ6 knockdown, endothelial Cyb5r3 KO mice

    PMID:34656824

    Open questions at the time
    • Electron-transfer mechanism between CYB5R3/CoQ and NOX4 not biochemically reconstituted
    • Reconciliation with ER pool of NOX4
  24. 2021 Medium

    NOX4-driven non-mitochondrial ROS was shown to activate PERK/eIF2α/ATF4 to promote autophagy and osteoclastogenesis, extending the UPR-autophagy axis to bone.

    Evidence Nox4 inhibitor and shRNA, NAC, PERK inhibitor, autophagy and osteoclastogenesis assays

    PMID:34650437

    Open questions at the time
    • Pharmacological inhibitor specificity
    • Direct UPR sensor target not identified
  25. 2021 Medium

    Neuronal NOX4 was found to impair autophagy-lysosomal flux and drive tau accumulation, linking the oxidase to tauopathy.

    Evidence Global KO and neuronal AAV knockdown, tauopathy mouse model, autophagy flux, behavior

    PMID:34922273

    Open questions at the time
    • Molecular redox target controlling autophagy flux not identified
    • Single model
  26. 2023 Medium

    IRP1 binding to IRE-like sequences in the NOX4 locus established an iron-sensing transcriptional input coupling iron overload to NOX4-driven ferroptosis.

    Evidence IRP1 binding assays on NOX4 promoter, iron loading, ferroptosis markers, Hepc1-/- mice with ferrostatin/DFO

    PMID:36738798

    Open questions at the time
    • IRE-like element function not validated by mutagenesis here
    • Direct vs indirect IRP1 effect
  27. 2024 Medium

    ISG15-mediated ISGylation stabilizing NOX4 against ubiquitin-proteasome degradation, controlled by DRD4, defined a post-translational stability switch in acute kidney injury.

    Evidence Transcriptomics, ISG15 manipulation, Co-IP for ISGylation/ubiquitination, stability assays, DRD4 KO/overexpression AKI models

    PMID:38354631

    Open questions at the time
    • ISGylation sites on NOX4 not mapped
    • E3 ligase mediating NOX4 ubiquitination unidentified
  28. 2024 Medium

    HOXD10 was shown to directly bind and repress the NOX4 promoter, and its hypermethylation de-represses NOX4 to drive TGF-β1-induced ferroptosis and renal fibrosis.

    Evidence ChIP, dual-luciferase, HOXD10 AAV overexpression, ferroptosis markers, bisulfite sequencing, UUO model

    PMID:38844470

    Open questions at the time
    • Single lab
    • Interaction with other NOX4 transcriptional regulators not integrated
  29. 2024 Medium

    NOX4 interaction with activated PKCα and ATF3-driven transcription was linked to ferroptosis of dopaminergic neurons in a Parkinson's model.

    Evidence Co-IP with PKCα, NOX4 inhibitor in MPTP mice, lipid peroxidation/iron assays, ATF3 analysis

    PMID:38993139

    Open questions at the time
    • Direct functional consequence of PKCα binding on NOX4 activity unclear
    • Single model and lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NOX4's multiple subcellular pools (ER, MAM, mitochondrial membranes) are coordinated, and how a single diffusible H2O2 output achieves the documented target selectivity (PP1, AKT, HDAC4, InsP3R), remains unresolved.
  • No atomic structure of human NOX4 to explain H2O2 vs O2- output
  • Mechanism conferring spatial confinement and target specificity of NOX4 H2O2 not defined
  • Reconciliation of ER vs inner/outer mitochondrial membrane localization claims

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005739 mitochondrion 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-9612973 Autophagy 4
Partners
CD44CYB5R3CYBAFYNHDAC4PPP1R15APRKCA

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 NOX4 encodes a ~65 kDa protein homologous to gp91phox (the catalytic subunit of the phagocyte NADPH oxidase), containing 5-6 conserved predicted transmembrane alpha-helices with putative heme-binding regions plus a flavoprotein homology domain with predicted FAD and NADPH binding sites, establishing it as an NADPH-dependent ROS-generating enzyme. cDNA cloning, sequence analysis, tissue expression (Northern blot/RT-PCR) Gene Medium 11376945
2003 Nox4-based NADPH oxidase, regulated upstream by Rac1 and arachidonic acid, mediates angiotensin II-induced ROS generation and downstream Akt/PKB activation and protein synthesis in mesangial cells. Antisense Nox4 knockdown abolished ANG II-induced NADPH oxidase activity and Akt/PKB activation, and dominant-negative Rac1 blocked Nox4-dependent ROS. Antisense oligonucleotide knockdown, dominant-negative Rac1 transfection, NADPH oxidase activity assay, ROS measurement, Akt phosphorylation assays, protein synthesis assay American journal of physiology. Renal physiology Medium 12842860
2005 Nox4 is the major source of NADPH-dependent ROS in the diabetic kidney; antisense-mediated Nox4 knockdown reduced NADPH oxidase activity in renal cortical/glomerular homogenates, blocked glucose-induced ROS in isolated glomeruli, and reduced downstream Akt/PKB and ERK1/2 activation, renal hypertrophy, and fibronectin expression. Antisense oligonucleotide administration in vivo (osmotic minipump), NADPH oxidase activity assay, ROS measurement from intact glomeruli, immunoblotting for Akt/ERK, histology for hypertrophy, fibronectin immunostaining The Journal of biological chemistry Medium 16135519
2005 NOX4-GFP fusion protein localizes to the endoplasmic reticulum in human endothelial cells (HUVECs), as shown by co-staining with an ER marker; distribution did not overlap with lysosomes, Weibel-Palade bodies, or mitochondria. Fluorescence confocal microscopy with ER, lysosomal, and mitochondrial markers; NOX4-GFP overexpression Antioxidants & redox signaling Medium 15706079
2006 NOX2 and NOX4 co-localize with the ER marker calreticulin in endothelial cells and interact with p22phox, as demonstrated by bimolecular fluorescence complementation; both NOX2 and NOX4 contribute equally to endothelial ROS production and proliferation. Bimolecular fluorescence complementation (BiFC) for NOX4-p22phox interaction, co-localization with calreticulin by immunofluorescence, siRNA knockdown, ROS measurement Antioxidants & redox signaling Medium 16987004
2008 Nox4 controls the switch between insulin-induced proliferation and differentiation in preadipocytes by regulating MAP kinase phosphatase-1 (MKP-1) expression; Nox4 siRNA reduced ROS and MKP-1, de-repressed ERK1/2, which phosphorylated IRS-1 at Ser612 to block differentiation and promote proliferation. siRNA knockdown, Nox4 overexpression, ERK1/2 phosphorylation assays, MKP-1 expression analysis, IRS-1 phosphorylation, proliferation/differentiation assays Arteriosclerosis, thrombosis, and vascular biology Medium 19057021
2009 Nox4 localizes to mitochondria in mesangial cells and kidney cortex; siRNA-mediated knockdown of Nox4 significantly reduces NADPH oxidase activity in purified mitochondria and blocks glucose-induced mitochondrial superoxide generation. Mitochondrial Nox4 expression is increased in diabetic kidney cortex. Subcellular fractionation, immunoblotting of mitochondrial fractions, immunofluorescence confocal with Mitotracker, MitoProt prediction, siRNA knockdown, NADPH oxidase activity assay in purified mitochondria, in vivo diabetic rat model Proceedings of the National Academy of Sciences of the United States of America Medium 19706525
2009 Structural elements in Nox4 determine both its subcellular localization to the ER and the type of ROS released (H2O2 extracellularly rather than O2-). The cytosolic tail of Nox4 confers constitutive activity (independent of cytosolic subunits), the N-terminal region determines ER localization, and the N-terminal part of Nox1 (but not Nox4) is cleaved. Replacing the Nox1 N-terminus with the Nox4 signal peptide redirected Nox1 from plasma membrane to vesicular structures and switched ROS from O2- to H2O2. Chimeric Nox1/Nox4 constructs expressed in HEK293 cells, TIRF microscopy, ROS type measurement, Myc-tagged Nox constructs, co-expression studies Antioxidants & redox signaling High 19061439
2010 NOX4 is required for PDGF-induced cell cycle entry in normal human fibroblasts; NOX4 knockdown did not block cyclin D1 upregulation but reduced ERK1 phosphorylation hours after stimulation and increased p53 and p21 levels. Co-knockdown of NOX4 with p53 or p21 rescued Rb phosphorylation, indicating NOX4 promotes cell cycle entry by suppressing a p53/p21 checkpoint. siRNA screen, Rb phosphorylation assay, cyclin D1/p53/p21 immunoblotting, co-knockdown epistasis Oncogene Medium 20531308
2011 Nox4 overexpression in cardiomyocytes in vivo activates the Nrf2 transcriptional pathway, leading to increased expression of antioxidant/detoxifying genes and elevated GSH and reduced:oxidized GSH ratio; these effects are abolished in Nrf2-null mice, demonstrating that Nox4-derived ROS activates Nrf2-dependent antioxidant defense. Transgenic mouse overexpression, microarray transcriptomics, Q-PCR, glutathione measurement, Nrf2 knockout genetic background Free radical biology & medicine Medium 21554947
2014 NOX4 silencing in VHL-deficient renal carcinoma cells abrogates nuclear accumulation of HIF2α and blocks cell branching, invasion, colony formation, and xenograft growth, demonstrating that NOX4-derived ROS is required for HIF2α nuclear localization and renal tumorigenesis. siRNA knockdown, ROS scavengers (TEMPOL, MnSOD/catalase overexpression), nuclear fractionation for HIF2α, in vitro invasion/colony assays, murine xenograft model Cancer research Medium 24755467
2014 NOX4 activity is increased in the ER (but not mitochondria) of cardiomyocytes during energy deprivation; NOX4-derived ROS activates the PERK-eIF2α-ATF4 pathway to induce autophagy, which preserves cellular energy and limits cell death. Subcellular fractionation, NOX4 knockdown/knockout, ER-specific ROS measurement, PERK/eIF2α/ATF4 pathway activation assays, autophagy flux measurement, cardiomyocyte viability Autophagy Medium 24492492
2015 FLT3ITD-driven leukemic transformation elevates NOX4 expression via STAT5-mediated activation of the NOX4 promoter; NOX4-derived ROS inactivates protein-tyrosine phosphatase DEP-1/PTPRJ, sustaining FLT3ITD signaling. Nox4 knockout hematopoietic progenitors are refractory to FLT3ITD transformation in vitro, and NOX4 downregulation attenuates myeloproliferative disease in vivo. NOX4 mRNA/protein quantification in FLT3ITD cells, STAT5 ChIP on NOX4 promoter, siRNA/knockout, DEP-1 PTP activity assay, ROS measurement, in vitro transformation assay, in vivo mouse disease models Leukemia High 26308771
2016 Nox4 regulates eIF2α-mediated stress signaling by binding to the PP1-targeting subunit GADD34 at the ER and inhibiting PP1 phosphatase activity through oxidation of its metal center (not thiol oxidation), thereby sustaining eIF2α phosphorylation and ATF4 levels. This is spatially confined to the ER and does not affect PP1 targets at other locations. Co-immunoprecipitation of Nox4 with GADD34, PP1 activity assays with metal center vs. thiol oxidation characterization, eIF2α phosphorylation/ATF4 immunoblotting, ER localization, genetic knockdown/overexpression, in vivo heart ischemia-reperfusion and acute kidney injury models The EMBO journal High 26742780
2016 FYN tyrosine kinase directly interacts with the C-terminal domain of NOX4 and phosphorylates it at tyrosine 566, negatively regulating NOX4-induced O2- production and apoptosis in cardiomyocytes. FYN and NOX4 co-localize in perinuclear mitochondria, ER, and nuclear fractions. FYN-deficient mice have exacerbated cardiac hypertrophy with increased ROS, rescued by Nox4 deletion. Co-immunoprecipitation, co-localization imaging, site-directed mutagenesis (Y566), NOX4 activity assay, Nox4-/- genetic rescue of FYN-/- cardiac phenotype, transverse aortic constriction model, human failing heart analysis The Journal of clinical investigation High 27525436
2017 In VEGF-stimulated endothelial cells, Nox4-derived H2O2 activates Nox2, which promotes mitochondrial ROS production via S36 phosphorylation of p66Shc; this Nox4/Nox2/pSer36-p66Shc/mtROS feed-forward axis drives sustained VEGFR2 phosphorylation, EC migration, and proliferation (angiogenesis). Cytosol/mitochondria-targeted RoGFP biosensors with real-time imaging, Nox4/Nox2 siRNA, mitochondria-targeted catalase overexpression, Nox4 overexpression, p66Shc(S36A) mutant, VEGFR2 tyrosine phosphorylation assay, EC migration/proliferation assays American journal of physiology. Cell physiology High 28424170
2017 NOX4 contains an ATP-binding motif; ATP directly binds and negatively regulates NOX4 activity. NOX4 localizes to the inner mitochondrial membrane, and subcellular redistribution of ATP from mitochondria acts as an allosteric switch to activate NOX4. NOX4-derived ROS inhibits PCAF-dependent acetylation and lysosomal degradation of PKM2. ATP-binding assay (identification of ATP-binding motif), subcellular fractionation for inner mitochondrial membrane localization, NOX4 activity assays with ATP titration, PKM2 acetylation/ubiquitination assays, PCAF interaction, NOX4 silencing in xenograft models Nature communications High 29051480
2018 NOX4-derived H2O2 in podocytes activates TRPC6-dependent calcium influx, contributing to podocyte damage in diabetic kidney disease; SSNox4-/- rats show lower basal intracellular Ca2+ in podocytes and less DKD-associated damage, and H2O2-stimulated TRPC-dependent calcium influx is blunted in Trpc6-knockout podocytes. Nox4 knockout rat (SSNox4-/-), TRPC6/TRPC5/6 knockout mice, H2O2 stimulation, live calcium imaging, electrophysiology patch-clamp, biosensor measurements, electron microscopy Journal of the American Society of Nephrology : JASN High 29793963
2019 CD44 directly associates with NOX4 in tachypaced atrial myocytes and atrial fibrillation patient tissues; blocking HAS/HA/CD44 signaling attenuates tachypacing-induced NOX4 expression, oxidative stress, and Ca2+-handling abnormalities (ox-CaMKII/p-RyR2). Co-immunoprecipitation of CD44 with NOX4, CD44-/- mice, anti-CD44 blocking antibody, Ca2+ spark measurement, tachypacing model in vitro and ex vivo, AF patient tissue analysis Journal of molecular and cellular cardiology Medium 31419440
2020 Nox4 upregulated at ER-mitochondria contact sites (MAMs) during stress inhibits InsP3 receptor-mediated Ca2+ transfer from ER to mitochondria by augmenting Akt-dependent phosphorylation of InsP3R, thereby reducing mitochondrial permeability transition and necrosis; in ischemia-reperfusion, Nox4 limits myocardial infarct size through this mechanism. MAM fractionation, Nox4 overexpression/knockout, InsP3R phosphorylation assays, mitochondrial Ca2+ measurement, mPT assay, cardiac ischemia-reperfusion model, cardiomyocyte/neuron stress models The EMBO journal High 33001475
2020 Nox4 is required for exercise-induced expression of metabolic genes (Ucp3, Hk2, Pdk4) in skeletal muscle; global and endothelial-specific Nox4 deletion impairs glucose and fatty acid oxidation after acute exercise, revealing an endothelium-to-skeletal muscle cross-talk mediated by Nox4-derived H2O2. Global and endothelial-specific Nox4 KO mice, 14C-labeled substrate oxidation assays ex vivo, qPCR/immunoblotting for metabolic genes, chronic exercise regimen with time-to-exhaustion measurement, catalase transgenic mice Molecular metabolism Medium 33400973
2020 SIRT1 loss in cachectic muscle induces NF-κB signaling that upregulates FOXO transcription factors and NOX4 expression; skeletal muscle-specific Nox4 knockout or pharmacological NOX4 blockade abrogates tumor-induced cachexia in mice, placing NOX4 downstream of the SIRT1/NF-κB/FOXO axis in muscle wasting. RNA-seq, Nox4 muscle-specific KO mice, pharmacological NOX4 inhibition, SIRT1 reconstitution, co-culture and in vivo cancer cachexia models The Journal of experimental medicine Medium 32441762
2020 Nox4 overexpression induces oxidation of HDAC4 in HEK293 cells and endothelial cells; Nox4-derived H2O2 increases HDAC4 phosphorylation at Ser632 and disrupts the HDAC4/Mef2A complex, de-repressing Mef2A and enabling proper endothelial tube formation. A redox-insensitive HDAC4 mutant blocks tube formation, while a redox-dead Nox4 mutant fails to rescue it. Tetracycline-inducible Nox4 overexpression in HEK293, HDAC4 oxidation assay, HDAC4/Mef2A co-immunoprecipitation, Ser632 phosphorylation analysis, redox-insensitive HDAC4 mutant, redox-dead Nox4 mutant, endothelial tube formation assay Redox biology High 32818796
2021 Nox4 promotes RANKL-induced autophagy and osteoclastogenesis by stimulating non-mitochondrial ROS production that activates the PERK/eIF-2α/ATF4 unfolded protein response pathway; inhibition of Nox4 or PERK/eIF-2α/ATF4 or ROS scavenging similarly blocks autophagy and osteoclastogenesis. Nox4 inhibitor (5-O-methyl quercetin), Nox4 shRNA knockdown, ROS scavenger (NAC), PERK inhibitor (GSK2606414), autophagy markers, osteoclastogenesis assays, pathway epistasis Frontiers in pharmacology Medium 34650437
2021 Neuronal NOX4 promotes pathological tau accumulation by impairing autophagy-lysosomal pathway flux; global Nox4 knockout and neuronal Nox4 knockdown in mice reduced accumulation of hyperphosphorylated tau, improved macroautophagy flux, reduced neurotoxicity, and prevented cognitive decline in a tauopathy model. Global Nox4 KO mice, neuronal-targeted AAV-mediated Nox4 knockdown, humanized tauopathy mouse model (AAV-TauP301L), tau immunohistochemistry, autophagy flux assays, behavioral testing Redox biology Medium 34922273
2021 NOX4 deletion in mice promotes cancerogen-induced tumor formation by reducing nuclear PP2A abundance; NOX4-derived H2O2 continuously oxidizes AKT, trapping PP2A in the cytosol, which maintains γH2AX (phospho-H2AX) levels for DNA damage recognition. Without Nox4, PP2A translocates to the nucleus, dephosphorylates γH2AX, impairing DNA damage recognition and simultaneously increasing AKT-driven proliferation. Nox4 KO mice, carcinogen-induced tumor models, AKT oxidation assay, PP2A subcellular fractionation, γH2AX immunostaining/immunoblotting, PP2A activity assay Proceedings of the National Academy of Sciences of the United States of America High 33836590
2021 CYB5R3 localizes to the mitochondrial outer membrane and directly interacts with NOX4; CYB5R3 activity and membrane translocation are required for optimal NOX4-dependent H2O2 generation via coenzyme Q (CoQ). Cyb5r3 knockdown reduces total H2O2 but increases mitochondrial O2•-, and cells lacking the CoQ-synthesizing enzyme COQ6 show decreased NOX4-derived H2O2. APEX2-based electron microscopy, proximity biotinylation, proximity ligation assay, Co-IP, CYB5R3 activity mutants, COQ6 knockdown, mitochondrial ROS species measurement, endothelium-specific Cyb5r3 KO mice Redox biology High 34656824
2023 NOX4 locus contains iron-response element-like (IRE-like) sequences bound and repressed by iron regulatory protein 1 (IRP1); excess iron dissociates IRP1 from these sequences, activating NOX4 transcription, which increases lipid peroxides and causes ferroptosis-associated mitochondrial dysfunction in osteoblasts. IRP1 binding assays on NOX4 promoter (IRE-like sequences), NOX4 expression analysis with iron loading, ferroptosis markers (lipid peroxides, MDA), mitochondrial morphology/function assays, ferroptosis inhibitor ferrostatin-1 and iron chelator DFO in Hepc1-/- mice Free radical biology & medicine Medium 36738798
2024 DRD4 reduces NOX4 expression via suppression of ISG15, which ISGylates NOX4 and stabilizes it; when DRD4 is active, ISG15 levels fall, NOX4 ISGylation decreases, ubiquitination of NOX4 increases, and NOX4 is degraded via the ubiquitin-proteasome pathway, reducing oxidative stress in acute kidney injury. Transcriptome sequencing, ISG15 knockdown/overexpression, Co-IP for NOX4 ISGylation and ubiquitination, NOX4 protein stability assays, DRD4 KO/overexpression in AKI models (IRI and cisplatin), oxidative stress measurement Redox biology Medium 38354631
2024 HOXD10 directly binds to the NOX4 promoter (confirmed by ChIP and dual-luciferase assay) and represses its transcription; HOXD10 overexpression attenuates TGF-β1-induced ferroptosis and renal fibrosis by reducing NOX4 expression and downstream ROS/lipid peroxide accumulation. HOXD10 is epigenetically silenced by hypermethylation in TGF-β1-treated cells. ChIP analysis, dual-luciferase reporter assay, HOXD10 overexpression (AAV in vivo), NOX4 expression assay, ferroptosis markers, bisulfite sequencing PCR for methylation, UUO fibrosis model Cell death & disease Medium 38844470
2024 NOX4 interacts with activated PKCα (protein kinase C alpha) to promote ferroptosis of dopaminergic neurons; NOX4 inhibition reduced lipid peroxidation, iron accumulation, and astrocytic lipocalin-2 expression (reducing neuroinflammation) in a Parkinson's disease MPTP model. ATF3 transcriptionally increases NOX4 expression in dopaminergic neurons and astrocytes. Co-immunoprecipitation of NOX4 with PKCα, NOX4 inhibitor in MPTP mouse model, lipid peroxidation and iron assays, behavioral tests, lipocalin-2 immunostaining, ATF3 transcriptional analysis Neural regeneration research Medium 38993139
2020 NOX4 (but not NOX2) activity and protein levels increase specifically in the ER of cardiomyocytes during energy deprivation; this ER-localized NOX4-derived ROS activates the PERK-eIF2α-ATF4 autophagy pathway, which is a critical adaptive response to energy stress. Organelle-specific NOX4 activity measurements (ER vs. mitochondria fractions), NOX4 genetic deletion, PERK/eIF2α/ATF4 pathway immunoblotting, autophagy markers, cardiomyocyte energy deprivation model Autophagy Medium 24492492
2004 Co-transfection of Nox4 with p22phox in osteoclasts enhances superoxide production and increases expression of cathepsin K and TRAP, with JNK activation and NF-κB inhibition, indicating p22phox is a necessary cofactor for Nox4 activity in osteoclasts. Nox4/p22phox co-transfection, superoxide assay, cathepsin K/TRAP expression, JNK/NF-κB signaling assays Journal of cellular biochemistry Low 15108351
2012 NOX4 produces H2O2 constitutively rather than superoxide (O2-), making it incapable of scavenging NO; Nox4 knockout mice on an ApoE-/- background develop increased atherosclerosis, and endothelial-specific (but not macrophage-specific) Nox4 deletion increases macrophage adhesion to endothelium, demonstrating an anti-atherosclerotic endothelial function of Nox4. Tamoxifen-inducible Nox4 KO crossed with ApoE-/- mice, partial carotid artery ligation model, atherosclerosis quantification, cell-type-specific KO, macrophage adhesion assay European heart journal Medium 26385958

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 681 11376945
2005 Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. The Journal of biological chemistry 434 16135519
2009 Subcellular localization of Nox4 and regulation in diabetes. Proceedings of the National Academy of Sciences of the United States of America 404 19706525
2005 Expression and localization of NOX2 and NOX4 in primary human endothelial cells. Antioxidants & redox signaling 272 15706079
2005 Neuronal expression of the NADPH oxidase NOX4, and its regulation in mouse experimental brain ischemia. Neuroscience 239 15802177
2003 Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells. American journal of physiology. Renal physiology 230 12842860
2008 Nox4 acts as a switch between differentiation and proliferation in preadipocytes. Arteriosclerosis, thrombosis, and vascular biology 210 19057021
2006 NOX2 and NOX4 mediate proliferative response in endothelial cells. Antioxidants & redox signaling 207 16987004
2017 ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis. American journal of physiology. Cell physiology 204 28424170
2017 NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance. Nature communications 174 29051480
2011 Nox4 regulates Nrf2 and glutathione redox in cardiomyocytes in vivo. Free radical biology & medicine 151 21554947
2015 The NADPH oxidase Nox4 has anti-atherosclerotic functions. European heart journal 146 26385958
2012 The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. American journal of respiratory cell and molecular biology 132 22904198
2009 Identification of structural elements in Nox1 and Nox4 controlling localization and activity. Antioxidants & redox signaling 125 19061439
2012 Neuroprotection after stroke by targeting NOX4 as a source of oxidative stress. Antioxidants & redox signaling 123 22937798
2018 A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease. Journal of the American Society of Nephrology : JASN 117 29793963
2016 Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2α-mediated stress signaling. The EMBO journal 103 26742780
2018 Nox4 in renal diseases: An update. Free radical biology & medicine 101 29969717
2015 The human Nox4: gene, structure, physiological function and pathological significance. Journal of drug targeting 90 25950600
2022 TRPM7 channel inhibition attenuates rheumatoid arthritis articular chondrocyte ferroptosis by suppression of the PKCα-NOX4 axis. Redox biology 88 35917680
2014 Nox4 and redox signaling mediate TGF-β-induced endothelial cell apoptosis and phenotypic switch. Cell death & disease 81 24457954
2014 The NADPH oxidase NOX4 inhibits hepatocyte proliferation and liver cancer progression. Free radical biology & medicine 79 24509161
2020 Nox4 regulates InsP3 receptor-dependent Ca2+ release into mitochondria to promote cell survival. The EMBO journal 77 33001475
2016 Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling. The Journal of clinical investigation 74 27525436
2023 Nox4 as a novel therapeutic target for diabetic vascular complications. Redox biology 73 37321060
2008 Nox4 oxidase overexpression specifically decreases endogenous Nox4 mRNA and inhibits angiotensin II-induced adventitial myofibroblast migration. Hypertension (Dallas, Tex. : 1979) 73 18474828
2018 Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling. Cardiovascular research 64 29040462
2020 SIRT1-NOX4 signaling axis regulates cancer cachexia. The Journal of experimental medicine 62 32441762
2004 Expression of Nox4 in osteoclasts. Journal of cellular biochemistry 62 15108351
2018 NOX4-driven ROS formation regulates proliferation and apoptosis of gastric cancer cells through the GLI1 pathway. Cellular signalling 61 29496628
2020 Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice. JCI insight 60 32544088
2014 NADPH oxidase NOX4 supports renal tumorigenesis by promoting the expression and nuclear accumulation of HIF2α. Cancer research 59 24755467
2022 Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma. Journal of cellular and molecular medicine 57 35023280
2021 Backstage players of fibrosis: NOX4, mTOR, HDAC, and S1P; companions of TGF-β. Cellular signalling 57 34438016
2015 NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells. Leukemia 56 26308771
2012 NOX4 pathway as a source of selective insulin resistance and responsiveness. Arteriosclerosis, thrombosis, and vascular biology 55 22328777
2021 Nox4 mediates skeletal muscle metabolic responses to exercise. Molecular metabolism 54 33400973
2020 Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis. Theranostics 54 32641980
2020 Nox (NADPH Oxidase) 1, Nox4, and Nox5 Promote Vascular Permeability and Neovascularization in Retinopathy. Hypertension (Dallas, Tex. : 1979) 53 32114846
2017 Nox4 regulates the eNOS uncoupling process in aging endothelial cells. Free radical biology & medicine 52 28916474
2015 The NADPH Oxidase Nox4 mediates tumour angiogenesis. Acta physiologica (Oxford, England) 50 26513738
2011 NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II. Molecular biology of the cell 50 21965295
2023 Osteoporotic bone loss from excess iron accumulation is driven by NOX4-triggered ferroptosis in osteoblasts. Free radical biology & medicine 48 36738798
2014 NOX4 regulates autophagy during energy deprivation. Autophagy 47 24492492
2016 Pro-atherogenic role of smooth muscle Nox4-based NADPH oxidase. Journal of molecular and cellular cardiology 45 26812119
2013 ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice. American journal of physiology. Renal physiology 45 23678045
2023 Cardiomyocyte NOX4 regulates resident macrophage-mediated inflammation and diastolic dysfunction in stress cardiomyopathy. Redox biology 44 37871532
1993 Duplicated KOX zinc finger gene clusters flank the centromere of human chromosome 10: evidence for a pericentric inversion during primate evolution. Nucleic acids research 42 8464732
2010 The NADPH oxidases NOX4 and DUOX2 regulate cell cycle entry via a p53-dependent pathway. Oncogene 41 20531308
2022 Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism. The Journal of clinical investigation 39 35617030
2019 Tubular NOX4 expression decreases in chronic kidney disease but does not modify fibrosis evolution. Redox biology 39 31247506
2022 NADPH Oxidase 4 (NOX4) in Cancer: Linking Redox Signals to Oncogenic Metabolic Adaptation. International journal of molecular sciences 37 35269843
2015 Nox-4 and progressive kidney disease. Current opinion in nephrology and hypertension 37 25402870
2015 Nox4 supports proper capillary growth in exercise and retina neo-vascularization. The Journal of physiology 37 25652847
2015 Role of smooth muscle Nox4-based NADPH oxidase in neointimal hyperplasia. Journal of molecular and cellular cardiology 37 26582463
2023 Mitochondria- and NOX4-dependent antioxidant defense mitigates progression to nonalcoholic steatohepatitis in obesity. The Journal of clinical investigation 35 38060313
2017 The Role of NOX4 and TRX2 in Angiogenesis and Their Potential Cross-Talk. Antioxidants (Basel, Switzerland) 35 28594389
2023 Metformin ameliorates ferroptosis in cardiac ischemia and reperfusion by reducing NOX4 expression via promoting AMPKα. Pharmaceutical biology 34 37288723
2022 The NADPH oxidase NOX4 regulates redox and metabolic homeostasis preventing HCC progression. Hepatology (Baltimore, Md.) 34 35920301
2021 Nox4 Promotes RANKL-Induced Autophagy and Osteoclastogenesis via Activating ROS/PERK/eIF-2α/ATF4 Pathway. Frontiers in pharmacology 34 34650437
2020 Circular RNA NOX4 promotes the development of colorectal cancer via the microRNA‑485‑5p/CKS1B axis. Oncology reports 34 32901890
2018 NADPH oxidase NOX4 is a glycolytic regulator through mROS-HIF1α axis in thyroid carcinomas. Scientific reports 34 30367082
2017 Endothelial Nox4-based NADPH oxidase regulates atherosclerosis via soluble epoxide hydrolase. Biochimica et biophysica acta. Molecular basis of disease 34 28185955
2017 Adventitial Fibroblast Nox4 Expression and ROS Signaling in Pulmonary Arterial Hypertension. Advances in experimental medicine and biology 34 29047077
2020 NOX4-dependent regulation of ENaC in hypertension and diabetic kidney disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 32799394
2022 NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells. Molecular oncology 32 35203105
2021 NOX4-derived ROS-induced overexpression of FOXM1 regulates aerobic glycolysis in glioblastoma. BMC cancer 32 34740322
2021 Role of Nox4 in High Calcium-Induced Renal Oxidative Stress Damage and Crystal Deposition. Antioxidants & redox signaling 31 34435888
2023 Targeting benign prostate hyperplasia treatments: AR/TGF-β/NOX4 inhibition by apocynin suppresses inflammation and proliferation. Journal of advanced research 29 37061215
2021 NOX4 Signaling Mediates Cancer Development and Therapeutic Resistance through HER3 in Ovarian Cancer Cells. Cells 29 34209278
2021 Implication of type 4 NADPH oxidase (NOX4) in tauopathy. Redox biology 29 34922273
2024 HOXD10 attenuates renal fibrosis by inhibiting NOX4-induced ferroptosis. Cell death & disease 28 38844470
2019 CSF-1 in Osteocytes Inhibits Nox4-mediated Oxidative Stress and Promotes Normal Bone Homeostasis. JBMR plus 28 32666016
2021 NOX4: a potential therapeutic target for pancreatic cancer and its mechanism. Journal of translational medicine 27 34930338
2018 NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD. BMC pulmonary medicine 27 29986678
2017 Nox4 genetic inhibition in experimental hypertension and metabolic syndrome. Archives of cardiovascular diseases 27 29113787
2014 Nuclear Nox4-derived reactive oxygen species in myelodysplastic syndromes. BioMed research international 27 24719867
2024 DRD4 alleviates acute kidney injury by suppressing ISG15/NOX4 axis-associated oxidative stress. Redox biology 26 38354631
2024 Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4. Journal of agricultural and food chemistry 26 38483540
2023 Ginsenoside Rg1 treatment alleviates renal fibrosis by inhibiting the NOX4-MAPK pathway in T2DM mice. Renal failure 26 37017270
2020 The role of NOX4 in pulmonary diseases. Journal of cellular physiology 26 32780450
2016 Nox4 and Duox1/2 Mediate Redox Activation of Mesenchymal Cell Migration by PDGF. PloS one 26 27110716
2014 Nox4-mediated cell signaling regulates differentiation and survival of neural crest stem cells. Molecules and cells 26 25410908
2021 Genetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors. Proceedings of the National Academy of Sciences of the United States of America 25 33836590
2019 Downregulated NOX4 underlies a novel inhibitory role of microRNA-137 in prostate cancer. Journal of cellular biochemistry 24 30637800
2014 Lentivirus-mediated Nox4 shRNA invasion and angiogenesis and enhances radiosensitivity in human glioblastoma. Oxidative medicine and cellular longevity 24 24868315
2023 TRIM-containing 44 aggravates cardiac hypertrophy via TLR4/NOX4-induced ferroptosis. Journal of molecular medicine (Berlin, Germany) 22 37119283
2020 Oxidation of HDAC4 by Nox4-derived H2O2 maintains tube formation by endothelial cells. Redox biology 22 32818796
2020 NADPH oxidase 4 (Nox4) deletion accelerates liver regeneration in mice. Redox biology 22 33493901
2019 Tachycardia-induced CD44/NOX4 signaling is involved in the development of atrial remodeling. Journal of molecular and cellular cardiology 22 31419440
2017 CRISPR-Cas9 Mediated NOX4 Knockout Inhibits Cell Proliferation and Invasion in HeLa Cells. PloS one 22 28099519
1993 Chromosomal localization of 9 KOX zinc finger genes: physical linkages suggest clustering of KOX genes on chromosomes 12, 16, and 19. Human genetics 22 8262519
2023 Diosgenin Inhibits ROS Generation by Modulating NOX4 and Mitochondrial Respiratory Chain and Suppresses Apoptosis in Diabetic Nephropathy. Nutrients 21 37432297
2022 MicroRNA-182-5p Attenuates Asthmatic Airway Inflammation by Targeting NOX4. Frontiers in immunology 21 35711428
2022 Intestinal microbiota regulates diabetes and cancer progression by IL-1β and NOX4 dependent signaling cascades. Cellular and molecular life sciences : CMLS 21 36040503
2022 Astragaloside IV ameliorates sepsis-induced myocardial dysfunction by regulating NOX4/JNK/BAX pathway. Life sciences 21 36302499
2021 Obesity increases neuropathic pain via the AMPK-ERK-NOX4 pathway in rats. Aging 21 34326272
2021 Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation. Redox biology 21 34656824
2013 Nox2 and Nox4 influence neonatal c-kit(+) cardiac precursor cell status and differentiation. American journal of physiology. Heart and circulatory physiology 21 23832701
2024 NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation. Neural regeneration research 20 38993139

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