Affinage

NKRF

NF-kappa-B-repressing factor · UniProt O15226

Round 2 corrected
Length
690 aa
Mass
77.7 kDa
Annotated
2026-04-29
130 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NKRF functions as a constitutive transcriptional repressor of NF-κB-driven proinflammatory gene expression by directly interacting with the NF-κB p65 subunit at target promoters, thereby suppressing transcription of genes such as IL-8 and iNOS (PMID:18025206). NKRF resides predominantly in nucleoli through an RNA-dependent retention mechanism and binds double-stranded RNA via a central domain, with actinomycin D treatment releasing it from nucleoli (PMID:15226370). NKRF expression is regulated post-transcriptionally: the RNA-binding protein HuR stabilizes NKRF mRNA through AU-rich elements (PMID:33330514), while multiple microRNAs—including miR-301a, miR-301a-3p, and miR-192—directly target the NKRF 3′UTR to suppress its expression, thereby derepressing NF-κB signaling in contexts of viral neuroinflammation, gastric cancer, and cisplatin resistance in lung cancer (PMID:31527198, PMID:32468020, PMID:34953057). SARS-CoV-2 NSP10 physically engages NKRF in a viral–host interactome, consistent with a mechanism whereby the virus relieves NKRF-mediated NF-κB repression to promote IL-8-driven inflammation (PMID:32838362).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2004 High

    The subnuclear localization and RNA-binding properties of NKRF were established, showing that constitutive nucleolar residence is RNA-dependent and that NKRF binds dsRNA through a central domain—raising the question of how a transcriptional repressor is sequestered away from its chromatin targets.

    Evidence GFP-tagged deletion mapping, FRAP, dsRNA-binding assays, and actinomycin D release in human cell lines

    PMID:15226370

    Open questions at the time
    • No identification of the specific RNA species mediating nucleolar retention
    • The functional consequence of dsRNA binding for NF-κB repression is unknown
    • No stimulus was found to alter localization, leaving the signal for nucleoplasmic redistribution unresolved
  2. 2007 High

    NKRF was shown to directly interact with NF-κB p65, and a synthetic peptide disrupting this interaction impaired IL-8 transcription in stimulated epithelial cells, establishing that the NKRF–p65 physical association is functionally required for transcriptional repression of at least one key NF-κB target gene.

    Evidence Tandem affinity purification identifying endogenous interaction, inhibitory peptide nucleofection with IL-8 transcription readout in IL-1- and H. pylori-stimulated epithelial cells

    PMID:18025206

    Open questions at the time
    • The structural basis of the NKRF–p65 interface beyond the peptide region is uncharacterized
    • It is unclear whether NKRF represses all NF-κB target genes or only a subset bearing specific negative regulatory elements
  3. 2013 Medium

    In vivo siRNA knockdown of NKRF in a ventilator-induced lung injury model recapitulated the anti-inflammatory effects of NF-κB inhibition, placing NKRF in the NF-κB-dependent inflammatory cascade in acute lung injury.

    Evidence Mouse VILI model with NKRF siRNA knockdown, SN50 NF-κB inhibitor, and iPSC therapy with readouts of MIP-2, neutrophil infiltration, and oxidative stress

    PMID:23840526

    Open questions at the time
    • The directionality of NKRF's role here (pro- versus anti-inflammatory) is paradoxical relative to its canonical repressive function—NKRF knockdown was protective, suggesting context-dependent activity
    • Mechanism by which NKRF would promote inflammation in this model is not resolved
    • Single laboratory observation without replication
  4. 2019 High

    miR-301a was identified as a direct suppressor of NKRF in JEV-infected microglia, establishing the first miRNA-mediated derepression mechanism for NF-κB through NKRF degradation, with in vivo rescue confirming physiological relevance in viral neuroinflammation.

    Evidence miR-301a gain/loss-of-function with NKRF overexpression rescue in vitro; in vivo miR-301a neutralization in mouse brain restoring NKRF and reducing neuroinflammation

    PMID:31527198

    Open questions at the time
    • Whether miR-301a-mediated NKRF suppression operates in non-CNS inflammatory contexts is untested
    • Quantitative threshold of NKRF depletion required to derepress NF-κB is unknown
  5. 2020 Medium

    Multiple converging studies expanded NKRF regulation and interactome: miR-301a-3p was validated as a direct NKRF-targeting miRNA in gastric cancer cells activating NF-κB; HuR was shown to stabilize NKRF mRNA via AU-rich elements, linking post-transcriptional NKRF maintenance to disc degeneration and inflammation; and SARS-CoV-2 NSP10 was identified as a physical interactor of NKRF, implicating viral hijacking of the NKRF–NF-κB axis in COVID-19 cytokine storm.

    Evidence Luciferase 3′UTR assay for miR-301a-3p (gastric cancer cells); RNA immunoprecipitation for HuR–NKRF mRNA binding plus in vivo rat IVDD rescue; AP-MS viral–host interactome for NSP10–NKRF

    PMID:32468020 PMID:32838362 PMID:33330514

    Open questions at the time
    • NSP10–NKRF interaction lacks mutagenesis or rescue validation
    • Whether HuR-mediated NKRF stabilization operates broadly or is tissue-specific (beyond NP cells) is unknown
    • Relative contributions of miR-301a-3p versus other miRNAs to NKRF suppression in gastric cancer are not quantified
  6. 2021 High

    miR-192 was validated as a third miRNA directly targeting NKRF, and its overexpression conferred cisplatin resistance in lung cancer cells through NF-κB derepression—an effect reversed by NF-κB inhibition—consolidating the paradigm that miRNA-mediated NKRF loss is a recurrent mechanism for pathological NF-κB activation.

    Evidence Luciferase reporter assay confirming miR-192/NKRF 3′UTR binding; gain/loss-of-function with curcumin-mediated NF-κB rescue in A549 lung cancer cells

    PMID:34953057

    Open questions at the time
    • Contribution of NKRF loss to cisplatin resistance in patient tumors is not validated
    • Whether miR-192-driven NKRF suppression cooperates with other miRNAs targeting NKRF in the same tumor is unknown
  7. 2021 Medium

    NKRF was positioned as a downstream effector in the CNTF/STAT3 signaling axis that inhibits neurotoxic A1 astrocyte transformation after spinal cord injury, extending NKRF's anti-inflammatory role beyond direct NF-κB repression to astrocyte polarization.

    Evidence miR-21a-5p manipulation and Cntfr-α siRNA in astrocytes and mouse TSCI model with A1/A2 marker quantification

    PMID:34345208

    Open questions at the time
    • NKRF-specific loss-of-function or gain-of-function in the astrocyte polarization phenotype was not directly tested
    • Whether NKRF acts through NF-κB repression or an independent mechanism in astrocytes is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the RNA species mediating NKRF nucleolar retention, the structural basis of the NKRF–p65 interaction, the mechanism by which NKRF selectively represses specific NF-κB target genes, and whether the dsRNA-binding activity of NKRF connects to innate immune RNA sensing pathways.
  • No structural model of NKRF or NKRF–p65 complex exists
  • The RNA ligands responsible for nucleolar retention have not been identified
  • Functional link between dsRNA binding and transcriptional repression is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 1 GO:0005730 nucleolus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
ELAVL1NSP10RELA

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 NRF (NKRF) localizes constitutively and predominantly to nucleoli via a large central domain, with only minor fractions in nucleoplasm and cytoplasm. FRAP analysis demonstrated that nucleolar localization correlates inversely with protein mobility. The N-terminal nuclear localization sequence drives nuclear accumulation of all N-terminal fragments, while C-terminal fragments also localize to the nucleus without a canonical NLS. Actinomycin D treatment releases NRF from nucleoli, suggesting RNA-dependent retention. NRF was found to bind double-stranded RNA (dsRNA), a property mapping to several fragments that overlap with the nucleolar affinity domain. Viral infection or LPS treatment did not alter this localization. GFP-tagging, fluorescence microscopy, FRAP analysis, deletion/fragment mapping, dsRNA binding assay, actinomycin D treatment Journal of cell science High 15226370
2007 NRF (NKRF) directly interacts with NF-κB p65 in cells, and a synthetic peptide corresponding to amino acids 223–238 of NRF interferes with endogenous p65 binding to NRF. Nucleofection of this inhibitory peptide into IL-1-stimulated cervical epithelial cells and Helicobacter pylori-infected gastric epithelial cells significantly decreased endogenous IL-8 gene transcription, demonstrating that the NRF/NF-κB interaction is required for IL-8 gene activation in response to these stimuli. Tandem affinity purification (TAP), synthetic inhibitory peptide nucleofection, IL-8 gene transcription assay in human cell lines Journal of immunology High 18025206
2013 In a mouse model of ventilator-induced lung injury (VILI), NF-κB and NKRF are both activated by high-tidal-volume mechanical ventilation. iPSC or iPSC-conditioned medium administration attenuated lung injury, neutrophil infiltration, MIP-2 production, and oxidative stress. Pharmacological inhibition of NF-κB (SN50) or siRNA-mediated knockdown of NKRF each mimicked the protective effects of iPSC therapy, suggesting NKRF activity contributes to ventilation-induced inflammation and that suppression of the NF-κB/NKRF pathway mediates iPSC-based lung protection. Mouse VILI model, siRNA knockdown of NKRF, NF-κB inhibitor SN50, iPSC/iPSC-CM administration, measurement of MIP-2, malondialdehyde, neutrophil infiltration, lung histology PloS one Medium 23840526
2019 In Japanese encephalitis virus (JEV)-infected microglial cells and human brain, NKRF was identified as a direct target of miR-301a. miR-301a upregulation suppresses NKRF expression, which releases NF-κB from NKRF-mediated inhibition, resulting in enhanced nuclear translocation of NF-κB and amplified proinflammatory cytokine production. NKRF overexpression in miR-301a-inhibited cells restored basal NF-κB nuclear accumulation. In vivo neutralization of miR-301a in mouse brain restored NKRF expression and reduced inflammatory response, microglial M1 activation, and neuronal apoptosis. miRNA overexpression/inhibition in microglial cells, NKRF overexpression rescue, NF-κB nuclear translocation assay, in vivo miR-301a neutralization in mouse brain, cytokine measurement, microglial activation assays Journal of immunology High 31527198
2020 NKRF was identified as a direct target of miR-301a-3p in human gastric cancer cells. Luciferase reporter assay confirmed miR-301a-3p binds the NKRF 3'UTR. Overexpression of miR-301a-3p suppressed NKRF expression, leading to increased NF-κB nuclear protein levels and transcriptional activation of NF-κB downstream targets. Conversely, modulating NKRF expression affected NF-κB signaling activity, proliferation, invasion, and migration of gastric cancer cells in vitro. Luciferase reporter assay (miR-301a-3p/NKRF 3'UTR), miRNA overexpression/knockdown, NF-κB reporter assay, Western blot, MTS proliferation assay, Transwell invasion/migration assay International journal of oncology Medium 32468020
2020 SARS-CoV-2 non-structural protein 10 (NSP10) interacts with NKRF (NF-κB-repressing factor) in a viral-host interactome screen. This interaction was proposed to facilitate IL-8 induction by relieving NKRF-mediated repression of NF-κB, potentially contributing to IL-8-mediated neutrophil chemotaxis and the cytokine storm observed in severe COVID-19. Genome-wide viral-host protein interaction screen (affinity purification/mass spectrometry), quantitative proteomics of COVID-19 PBMCs Med Medium 32838362
2020 RNA-binding protein HuR stabilizes NKRF mRNA by binding to AU-rich elements (AREs) in NKRF mRNA, maintaining NKRF protein levels. In TNF-α-treated nucleus pulposus (NP) cells and degenerative NP tissue, HuR expression is decreased, leading to reduced NKRF stability and consequent NF-κB pathway activation. NKRF overexpression suppressed inflammation (TNF-α-induced) and extracellular matrix degradation in HuR-deficient NP cells. In vivo, NKRF overexpression (but not HuR overexpression) ameliorated intervertebral disc degeneration in rats. RNA immunoprecipitation (RIP) for HuR-NKRF mRNA interaction, NKRF overexpression rescue in HuR-knockdown cells, in vivo rat IVDD model with NKRF overexpression, Western blot, NF-κB pathway assays Frontiers in cell and developmental biology High 33330514
2021 In a traumatic spinal cord injury (TSCI) model, miR-21a-5p is upregulated and suppresses Cntfr-α expression. CNTF signaling via its receptor activates a CNTF/STAT3/Nkrf pathway that inhibits naïve astrocyte transformation into neurotoxic A1 reactive astrocytes. Downregulation of miR-21a-5p reduced A1 marker expression, and Cntfr-α siRNA reversed this effect. The study identifies NKRF as a downstream effector in the CNTF/STAT3 signaling axis that modulates neuroinflammatory astrocyte polarization. miR-21a-5p overexpression/inhibition in astrocytes and in vivo TSCI mouse model, Cntfr-α siRNA, A1/A2 astrocyte marker quantification, luciferase reporter confirming miR-21a-5p/Cntfr-α binding site International journal of biological sciences Medium 34345208
2021 miR-192 directly targets NKRF in lung cancer cells, as validated by luciferase reporter assay. Overexpression of miR-192 in cisplatin-sensitive A549 cells suppressed NKRF expression, increased nuclear NF-κB protein and transcriptional activity, and upregulated anti-apoptotic NF-κB targets (cIAP1, cIAP2, Bcl-xl, XIAP), conferring cisplatin resistance. Inhibition of NF-κB signaling by curcumin reversed these effects, confirming that miR-192 promotes cisplatin resistance specifically through the NKRF/NF-κB axis. miRNA microarray, qRT-PCR validation, luciferase reporter assay (miR-192/NKRF 3'UTR), gain/loss-of-function studies, NF-κB nuclear protein and transcriptional activity assays, Western blot for anti-apoptotic proteins, NF-κB inhibitor rescue Thoracic cancer High 34953057

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2012 TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell metabolism 516 22560223
2015 SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free radical biology & medicine 477 26232625
2001 Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. American journal of physiology. Endocrinology and metabolism 449 11701451
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. Journal of proteome research 422 20020773
2002 Functional proteomic analysis of human nucleolus. Molecular biology of the cell 391 12429849
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2009 Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging cell 292 19575768
2020 Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (New York, N.Y.) 291 32838362
2011 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity 286 21903422
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2017 Energy stress-induced lncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development. Nature communications 178 28978906
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2018 OTUB2 Promotes Cancer Metastasis via Hippo-Independent Activation of YAP and TAZ. Molecular cell 163 30472188
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2012 Mitochondrial SKN-1/Nrf mediates a conserved starvation response. Cell metabolism 156 23040073
2013 Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. PLoS genetics 146 24068940
2018 Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration. Redox biology 144 30253279
2010 PGC-1 beta-regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha. Mitochondrion 126 20561910
2013 Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway. Nutrition & metabolism 123 23311701
2017 Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy. Toxicology reports 105 28959654
2015 Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling. British journal of cancer 95 26469832
2022 Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation. International journal of molecular sciences 86 35409364
2018 Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer. Cancers 75 30257470
2011 Overexpression of TFAM, NRF-1 and myr-AKT protects the MPP(+)-induced mitochondrial dysfunctions in neuronal cells. Biochimica et biophysica acta 71 21856379
2015 MicroRNA-153/Nrf-2/GPx1 pathway regulates radiosensitivity and stemness of glioma stem cells via reactive oxygen species. Oncotarget 64 26124081
2022 Fetuin-A alleviates neuroinflammation against traumatic brain injury-induced microglial necroptosis by regulating Nrf-2/HO-1 pathway. Journal of neuroinflammation 63 36333786
2012 Paraquat induces lung alveolar epithelial cell apoptosis via Nrf-2-regulated mitochondrial dysfunction and ER stress. Archives of toxicology 60 22678742
2014 MicroRNAs mediate dietary-restriction-induced longevity through PHA-4/FOXA and SKN-1/Nrf transcription factors. Current biology : CB 59 25242029
2016 Intranasal insulin improves cerebral blood flow, Nrf-2 expression and BDNF in STZ (ICV)-induced memory impaired rats. Life sciences 54 27693383
2023 Cigarette smoke induces the ROS accumulation and iNOS activation through deactivation of Nrf-2/SIRT3 axis to mediate the human bronchial epithelium ferroptosis. Free radical biology & medicine 51 36871899
2017 A novel antioxidant peptide, purified from Bacillus amyloliquefaciens, showed strong antioxidant potential via Nrf-2 mediated heme oxygenase-1 expression. Food chemistry 49 28873597
2022 Icariin protects vertebral endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 pathway. Frontiers in pharmacology 48 36176424
2017 Effects of Estradiol on Autophagy and Nrf-2/ARE Signals after Cerebral Ischemia. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 28419990
2020 Empagliflozin ameliorates ethanol-induced liver injury by modulating NF-κB/Nrf-2/PPAR-γ interplay in mice. Life sciences 46 32512011
2021 miR-21a-5p Promotes Inflammation following Traumatic Spinal Cord Injury through Upregulation of Neurotoxic Reactive Astrocyte (A1) Polarization by Inhibiting the CNTF/STAT3/Nkrf Pathway. International journal of biological sciences 44 34345208
2018 Dimethyl fumarate ameliorates acetaminophen-induced hepatic injury in mice dependent of Nrf-2/HO-1 pathway. Life sciences 41 30550888
2016 Lovastatin protects neurite degeneration in LRRK2-G2019S parkinsonism through activating the Akt/Nrf pathway and inhibiting GSK3β activity. Human molecular genetics 40 26931464
2004 Alpha-Pal/NRF-1 regulates the promoter of the human integrin-associated protein/CD47 gene. The Journal of biological chemistry 40 14747477
2004 Nucleolar localization and mobility analysis of the NF-kappaB repressing factor NRF. Journal of cell science 39 15226370
2019 miR-301a Regulates Inflammatory Response to Japanese Encephalitis Virus Infection via Suppression of NKRF Activity. Journal of immunology (Baltimore, Md. : 1950) 38 31527198
2021 Probucol attenuates NF-κB/NLRP3 signalling and augments Nrf-2 mediated antioxidant defence in nerve injury induced neuropathic pain. International immunopharmacology 37 34891000
2019 Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats. Pharmacology 37 31344704
2023 Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway. International immunopharmacology 36 37054647
2021 Enterocyte synthesizes and secrets uric acid as antioxidant to protect against oxidative stress via the involvement of Nrf pathway. Free radical biology & medicine 36 34954337
2021 Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2/NF-κB Pathway in Transgenic Mouse Model. International journal of molecular sciences 35 34203049
2020 The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf-2, NF-kB and apoptotic pathway. Journal of food biochemistry 35 32250487
2017 Nrf-2-driven long noncoding RNA ODRUL contributes to modulating silver nanoparticle-induced effects on erythroid cells. Biomaterials 35 28351005
2020 NRF-2 and nonalcoholic fatty liver disease. Annals of hepatology 33 31959521
2020 HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration. Molecular neurobiology 32 32978730
2017 Identification, characterization, and function analysis of the NF-κB repressing factor (NKRF) gene from Litopenaeus vannamei. Developmental and comparative immunology 32 28564581
2021 Therapeutic potential of Nrf-2 pathway in the treatment of diabetic neuropathy and nephropathy. Molecular biology reports 31 33754251
2016 Daphnetin ameliorates 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis through Nrf-2-Keap1 and NF-κB pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 27470383
2007 Icariin promotes expression of PGC-1alpha, PPARalpha, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro. Acta pharmacologica Sinica 30 17883938
2004 Occupancy and synergistic activation of the FMR1 promoter by Nrf-1 and Sp1 in vivo. Human molecular genetics 30 15175277
2024 Quercetin Modulates Ferroptosis via the SIRT1/Nrf-2/HO-1 Pathway and Attenuates Cartilage Destruction in an Osteoarthritis Rat Model. International journal of molecular sciences 28 39000568
2018 AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress. Molecular neurobiology 26 30267375
2023 Activation of the Nrf-2 pathway by pinocembrin safeguards vertebral endplate chondrocytes against apoptosis and degeneration caused by oxidative stress. Life sciences 25 37820754
2022 Molecular mechanisms regulating the pharmacological actions of icariin with special focus on PI3K-AKT and Nrf-2 signaling pathways. Molecular biology reports 25 35941411
2017 Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA. Current cardiology reviews 25 28215178
2017 Duloxetine Protects Human Neuroblastoma Cells from Oxidative Stress-Induced Cell Death Through Akt/Nrf-2/HO-1 Pathway. Neurochemical research 25 29134401
2015 NT-020 treatment reduces inflammation and augments Nrf-2 and Wnt signaling in aged rats. Journal of neuroinflammation 25 26376629
2007 NRF-1, and AP-1 regulate the promoter of the human calpain small subunit 1 (CAPNS1) gene. Gene 25 18234454
2005 Role of the nrf-2 gene in protection and repair of gastric mucosa against oxidative stress. Inflammopharmacology 25 16259730
2020 Intellectual disability-associated factor Zbtb11 cooperates with NRF-2/GABP to control mitochondrial function. Nature communications 24 33122634
2002 Upregulation and activation of the Nrf-1 transcription factor in the lesioned hippocampus. The European journal of neuroscience 24 12059978
2015 What is Known Regarding the Participation of Factor Nrf-2 in Liver Regeneration? Cells 23 26010752
2014 Transcriptional regulation of the p73 gene by Nrf-2 and promoter CpG methylation in human breast cancer. Oncotarget 23 25071010
2023 D-chiro-inositol increases antioxidant capacity and longevity of Caenorhabditis elegans via activating Nrf-2/SKN-1 and FOXO/DAF-16. Experimental gerontology 22 36921677
2023 β-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury. Molecular medicine (Cambridge, Mass.) 22 38049750
2020 Mesenchymal stem cell exosomes reverse acute lung injury through Nrf-2/ARE and NF-κB signaling pathways. PeerJ 22 32999767
2014 Elevated Expression of Nrf-2 and ABCG2 Involved in Multi-drug Resistance of Lung Cancer SP Cells. Drug research 22 25368906
2013 Effectiveness of miltefosine treatment in targeting anti-leishmanial HO-1/Nrf-2-mediated oxidative responses in visceral leishmaniasis patients. The Journal of antimicrobial chemotherapy 22 23729024
2023 Bdnf-Nrf-2 crosstalk and emotional behavior are disrupted in a sex-dependent fashion in adolescent mice exposed to maternal stress or maternal obesity. Translational psychiatry 21 38105264
2022 Targeting endoplasmic reticulum stress, Nrf-2/HO-1, and NF-κB by myristicin and its role in attenuation of ulcerative colitis in rats. Life sciences 21 36403646
2021 Wogonin Inhibits Cardiac Hypertrophy by Activating Nrf-2-Mediated Antioxidant Responses. Cardiovascular therapeutics 21 34290825
2021 MiR-192/NKRF axis confers lung cancer cell chemoresistance to cisplatin via the NF-κB pathway. Thoracic cancer 21 34953057
2020 Imperatorin Relieved Ulcerative Colitis by Regulating the Nrf-2/ARE/HO-1 Pathway in Rats. Inflammation 21 33098052
2019 Gastrodin alleviates Tourette syndrome via Nrf-2/HO-1/HMGB1/NF-кB pathway. Journal of biochemical and molecular toxicology 21 31468582
2018 Tetramethylpyrazine in a Murine Alkali-Burn Model Blocks NFκB/NRF-1/CXCR4-Signaling-Induced Corneal Neovascularization. Investigative ophthalmology & visual science 21 29801148
2018 Divergent Nrf Family Proteins and MtrCAB Homologs Facilitate Extracellular Electron Transfer in Aeromonas hydrophila. Applied and environmental microbiology 21 30266730
2016 Plumbagin protects against hydrogen peroxide-induced neurotoxicity by modulating NF-κB and Nrf-2. Archives of medical science : AMS 21 30154895
2015 Plumbagin protects against glucocorticoid-induced osteoporosis through Nrf-2 pathway. Cell stress & chaperones 21 25939783
2022 Pharmacological mechanism of xanthoangelol underlying Nrf-2/TRPV1 and anti-apoptotic pathway against scopolamine-induced amnesia in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 35658216
2021 Biochanin A attenuates obesity cardiomyopathy in rats by inhibiting oxidative stress and inflammation through the Nrf-2 pathway. Archives of physiology and biochemistry 20 33471570
2021 Sulforaphane alleviates hepatic ischemia-reperfusion injury through promoting the activation of Nrf-2/HO-1 signaling. Transplant immunology 20 34320386
2014 APE1 promotes antioxidant capacity by regulating Nrf-2 function through a redox-dependent mechanism. Free radical biology & medicine 20 25452143
2013 Suppressing NF-κB and NKRF Pathways by Induced Pluripotent Stem Cell Therapy in Mice with Ventilator-Induced Lung Injury. PloS one 20 23840526
2007 Peptide-mediated disruption of NFkappaB/NRF interaction inhibits IL-8 gene activation by IL-1 or Helicobacter pylori. Journal of immunology (Baltimore, Md. : 1950) 20 18025206
2023 Fenofibrate and Diosmetin in a rat model of testicular toxicity: New insight on their protective mechanism through PPAR-α/NRF-2/HO-1 signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 37413905
2020 Geniposide attenuates dextran sulfate sodium-induced colitis in mice via Nrf-2/HO-1/NF-κB pathway. Annals of palliative medicine 19 32787366
2015 Esculentoside A Attenuates Allergic Airway Inflammation via Activation of the Nrf-2 Pathway. International archives of allergy and immunology 19 26496193
2021 Astaxanthin attenuates acute cerebral infarction via Nrf-2/HO-1 pathway in rats. Current research in translational medicine 18 33476935
2019 Angelicae Gigantis Radix Regulates LPS-Induced Neuroinflammation in BV2 Microglia by Inhibiting NF-κB and MAPK Activity and Inducing Nrf-2 Activity. Molecules (Basel, Switzerland) 18 31635294
2017 Plumbagin prevents osteoarthritis in human chondrocytes through Nrf-2 activation. Molecular medicine reports 18 28259976
2015 Caenorhabditis elegans OSM-11 signaling regulates SKN-1/Nrf during embryonic development and adult longevity and stress response. Developmental biology 18 25637691
2022 Nicotinic Acid Riboside Regulates Nrf-2/P62-Related Oxidative Stress and Autophagy to Attenuate Doxorubicin-Induced Cardiomyocyte Injury. BioMed research international 17 35242876
2021 Activated Nrf-2 Pathway by Vitamin E to Attenuate Testicular Injuries of Rats with Sub-chronic Cadmium Exposure. Biological trace element research 17 34173155
2011 Nrf-2 regulates cyclosporine-stimulated HO-1 expression in gingiva. Journal of dental research 17 21622902
2024 Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway. Pesticide biochemistry and physiology 16 38879343
2023 Combination of metformin and hesperidin mitigates cyclophosphamide-induced hepatotoxicity. Emerging role of PPAR-γ/Nrf-2/NF-κB signaling pathway. International immunopharmacology 16 36812672
2021 Upregulation of NOX-2 and Nrf-2 Promotes 5-Fluorouracil Resistance of Human Colon Carcinoma (HCT-116) Cells. Biochemistry. Biokhimiia 16 33838628
2021 Temporal requirements of SKN-1/NRF as a regulator of lifespan and proteostasis in Caenorhabditis elegans. PloS one 16 34197476
2020 Upregulation of miRNA‑301a‑3p promotes tumor progression in gastric cancer by suppressing NKRF and activating NF‑κB signaling. International journal of oncology 16 32468020
2018 Exenatide Increases IL-1RA Concentration and Induces Nrf-2‒Keap-1‒Regulated Antioxidant Enzymes: Relevance to β-Cell Function. The Journal of clinical endocrinology and metabolism 16 29346597
2018 δ-Opioid Receptor-Nrf-2-Mediated Inhibition of Inflammatory Cytokines in Neonatal Hypoxic-Ischemic Encephalopathy. Molecular neurobiology 16 30560518
2022 Protection Against Drug-Induced Liver Injuries Through Nutraceuticals via Amelioration of Nrf-2 Signaling. Journal of the American Nutrition Association 15 35771985
2020 RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration. Frontiers in cell and developmental biology 15 33330514
2019 Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB. Journal of immunology research 15 31183386
2017 HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia. Scientific reports 15 28993637
2022 Effects of NRF-1 and PGC-1α cooperation on HIF-1α and rat cardiomyocyte apoptosis under hypoxia. Gene 14 35569770