Affinage

HMOX1

Heme oxygenase 1 · UniProt P09601

Length
288 aa
Mass
32.8 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HMOX1 encodes the inducible 32-kDa microsomal enzyme heme oxygenase-1 (HO-1), which catalyzes the regiospecific oxidative degradation of heme to carbon monoxide, ferrous iron (Fe²⁺), and biliverdin, distinguishing it from the constitutive, inducer-unresponsive HO-2 isoform (PMID:23746277). HMOX1 transcription is a major node of stress-responsive gene regulation: the antioxidant pathway transcription factor Nrf2 binds ARE elements in the HMOX1 promoter to drive its induction (PMID:27023064), with Nrf2 activity itself tuned by upstream signaling and stabilizing partners including ERK signaling (PMID:21622902), Mkp-1 (PMID:30061089), and SIAH2 (PMID:32042051), and by CD163-mediated hemoglobin scavenging in macrophages (PMID:30014796). Additional sequence-specific activators converge on the promoter and enhancer, including EGR-1 during cigarette-smoke exposure (PMID:20417178), HSF4 in lens epithelium (PMID:29454088), FOSL1 (PMID:39923427), an IFI16–JUND–SP1 complex acting through the IFI16 pyrin domain (PMID:39890789), and a HIF-1α/P53 versus HIF-1α/P300 competitive switch (PMID:37415103); epigenetic and post-transcriptional layers add Kat2a-driven histone acetylation at the promoter (PMID:30014796, PMID:38858351) and YTHDF2-mediated m6A-dependent decay of Hmox1 mRNA (PMID:36801705). At the protein level, HO-1 abundance is set by ubiquitin-dependent turnover: SIAH2 directs proteasomal degradation (PMID:32042051), the K243-linked ubiquitinated pool is reversed by USP7-mediated deubiquitination and stabilization under oxidative stress (PMID:35821281, PMID:37257587), and the lncRNA RGMB-AS1 shields HO-1 from TRC8-mediated ubiquitination (PMID:38574881). Through its Fe²⁺-liberating catalytic activity HO-1 is a central determinant of ferroptosis, where forced expression raises intracellular Fe²⁺ and lipid peroxidation and knockdown attenuates iron-dependent cell death across diverse cell types (PMID:36300537, PMID:36773431, PMID:34508760). HO-1 also performs catalysis-independent functions: it scaffolds IRF3 phosphorylation in innate immune signaling (PMID:21842368), and ER-anchored full-length HO-1 disrupts STING polymerization while a cleaved nuclear fragment binds cGAS to suppress its export and cGAMP production, broadly inhibiting the cGAS/STING type-I interferon pathway (PMID:39621310). In addition, HO-1 governs mitochondrial quality control via an Nrf-1/Pink1/Parkin mitophagy program (PMID:28194437) and, through direct interaction with LDHB, enables LONP1-mediated TFAM degradation driving mitochondrial dysfunction and ferroptosis in foamy macrophages (PMID:39731912). A transgenic study links astrocytic HMOX1 overexpression to α-synuclein accumulation and dopaminergic dysfunction (PMID:31180611).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 Medium

    Established that HO-1 activity is functionally required downstream of a physiological stimulus, showing prolactin-induced VEGF release in macrophages depends on HO activity.

    Evidence Pharmacological HO inducer/inhibitor and VEGF ELISA in human macrophages

    PMID:15352176

    Open questions at the time
    • No direct binding or genetic evidence linking HO-1 to VEGF machinery
    • Mechanism connecting CO/biliverdin to VEGF unresolved
  2. 2009 Medium

    Revealed a non-enzymatic scaffold function: HO-1 complexes with IRF3 and is required for its phosphorylation and type-I interferon induction in myeloid cells.

    Evidence Co-IP and myeloid-specific Hmox1 knockout mice with gene expression readouts

    PMID:21842368

    Open questions at the time
    • Structural basis of HO-1–IRF3 interaction undefined
    • Single-laboratory report
    • Relationship between scaffold and catalytic roles unresolved
  3. 2009 Medium

    Distinguished iron-induced HMOX1 upregulation as Nrf2-dependent rather than Bach1-dependent, refining the regulatory logic of iron sensing.

    Evidence Nrf2 siRNA knockdown and deferoxamine controls in HCV-expressing hepatoma cells

    PMID:19777608

    Open questions at the time
    • Direct ARE occupancy not measured in this context
    • Single laboratory
  4. 2010 Medium

    Identified EGR-1 as a context-specific activator of HO-1 in cigarette-smoke responses, broadening the transcription factor repertoire beyond Nrf2.

    Evidence Reporter assay with EGR-1 binding site, Egr-1 knockout MEFs, in vivo CS exposure

    PMID:20417178

    Open questions at the time
    • Interplay between EGR-1 and Nrf2 at the locus undefined
    • Single laboratory
  5. 2015 High

    Placed HO-1 downstream of progesterone in maternal-fetal immune tolerance, linking promoter methylation to CD8+ T cell tolerance and fetal growth.

    Evidence Progesterone receptor and Hmox1 knockout mice, promoter methylation, progesterone rescue

    PMID:25774501

    Open questions at the time
    • Molecular link between HO-1 products and tolerogenic T cell induction unresolved
    • Specific methyltransferase not identified
  6. 2016 Medium

    Demonstrated HO-1 is a direct Nrf2/ARE target gene contributing to a coordinated antioxidant transcriptional program and chemoresistance.

    Evidence Nrf2 ARE ChIP/binding assay and HO-1 siLencing with GSH depletion in neuroblastoma

    PMID:27023064

    Open questions at the time
    • Relative contribution of HO-1 versus other Nrf2 targets unresolved
    • Single laboratory
  7. 2017 High

    Defined a cytoprotective role for HO-1 in mitochondrial quality control, acting through the Pgc-1α/NRF-1 axis to enable Pink1/Park2-mediated mitophagy.

    Evidence Cardiomyocyte-specific Hmox1 knockout, EM, LC3II immunoblotting, NRF-1 promoter binding

    PMID:28194437

    Open questions at the time
    • Whether the effect requires catalysis versus protein function not separated
    • Direct HO-1 input to NRF-1 unresolved
  8. 2018 Medium

    Expanded the activating transcription factor set with HSF4 binding a defined HSE in the HMOX1 promoter in lens epithelium.

    Evidence Luciferase reporter with promoter mapping and HSF4 siRNA knockdown

    PMID:29454088

    Open questions at the time
    • In vivo relevance not tested
    • Single laboratory
  9. 2018 Medium

    Established positive feedback regulators of the Nrf2-HO-1 axis (Mkp-1 stabilizing Nrf2; CD163-Nrf2-HO-1-IL-10 macrophage switching), explaining amplification of HO-1 induction.

    Evidence Co-IP with DIDLID motif mapping and Mkp-1 KO mice; CD163 receptor signaling and Nrf2 translocation in macrophages

    PMID:30014796 PMID:30061089

    Open questions at the time
    • CD163 axis derived partly from review-level synthesis
    • Direct HO-1 promoter occupancy by these factors not the focus
  10. 2019 Medium

    Linked astrocytic HMOX1 overexpression to neurodegenerative pathology via miR-153/miR-223 downregulation and α-synuclein accumulation, and to mitochondrial iron-driven oxidative injury.

    Evidence GFAP.HMOX1 transgenic mice, miRNA profiling, α-synuclein siRNA rescue, neuron-astrocyte co-culture; HO-1 overexpression with mitochondrial iron and MPT pore assays

    PMID:19874266 PMID:31180611

    Open questions at the time
    • Overexpression models may not reflect endogenous levels
    • Mechanism linking HO-1 to specific miRNAs undefined
  11. 2020 High

    Identified SIAH2 as the E3 ligase driving proteasomal HO-1 degradation, with a dual effect via direct degradation and Nrf2-mediated transcription.

    Evidence SIAH2 KO mice and CRISPR human cells, RING-dependent Co-IP, proteasome inhibitor experiments

    PMID:32042051

    Open questions at the time
    • Specific HO-1 ubiquitination site by SIAH2 not pinpointed here
    • Tissue selectivity of the effect unexplained
  12. 2022 High

    Defined the deubiquitination arm of HO-1 stability control, showing USP7 binds HO-1 and reverses K243 ubiquitination to stabilize it under oxidative stress.

    Evidence Co-IP, ubiquitination assay with K243/K476 site mutagenesis, USP7 depletion, in vivo tumor and HCC specimen correlation

    PMID:35821281

    Open questions at the time
    • Whether USP7 antagonizes SIAH2 directly not tested
    • Trigger for USP7 K476 ubiquitination unresolved
  13. 2023 High

    Established HO-1 catalytic activity as a direct pro-ferroptotic driver through Fe²⁺ liberation, generalizing across multiple cell types and disease contexts.

    Evidence CRISPR knockout, overexpression, siRNA with direct Fe²⁺ and lipid peroxidation measurement in lens, ovarian cancer, and endothelial cells

    PMID:34508760 PMID:36300537 PMID:36773431

    Open questions at the time
    • Determinants of pro-ferroptotic versus cytoprotective outcome incompletely defined
    • Downstream lipid peroxidation effectors not mapped
  14. 2023 Medium

    Added post-transcriptional and replicated post-translational stability controls: YTHDF2-driven m6A decay of Hmox1 mRNA and a second USP7-HMOX1 stabilization context.

    Evidence Myeloid Ythdf2 KO with mRNA stability assay and Hmox1 inhibitor rescue; Co-IP and deubiquitination in SCI rat model

    PMID:36801705 PMID:37257587

    Open questions at the time
    • m6A sites on Hmox1 transcript not mapped
    • Generalizability of USP7 axis across tissues partial
  15. 2024 High

    Uncovered comprehensive catalysis-independent suppression of innate immunity by HO-1, both blocking STING polymerization/ER-to-Golgi transport and, as a cleaved nuclear fragment, inhibiting cGAS nuclear export.

    Evidence Unbiased CRISPR screen, STING polymerization and COPII transport assays, nuclear fractionation, cGAS Co-IP, cGAMP quantification, in vivo radiotherapy

    PMID:39621310

    Open questions at the time
    • Protease generating the cleaved HO-1 fragment not identified
    • Balance between enzymatic and immune-suppressive roles unresolved
  16. 2024 High

    Defined a direct HMOX1-LDHB interaction that couples HO-1 to mitochondrial dysfunction via LONP1-mediated TFAM degradation in foamy macrophages.

    Evidence scRNA/bulk RNA-seq, reciprocal Co-IP, LONP1 inhibitor and MitoTEMPO rescue, mouse atherosclerosis model

    PMID:39731912

    Open questions at the time
    • Structural interface of HMOX1-LDHB undefined
    • Whether catalysis is required for the interaction unresolved
  17. 2024 Medium

    Mapped additional transcriptional and protein-interaction control nodes: an IFI16-JUND-SP1 activating complex, FOSL1 promoter binding, HIF-1α/P53 versus P300 switching, Kat2a histone acetylation, PTGDS interaction, and a druggable HO-1 protein interface (H25A/K18A residues).

    Evidence Co-IP with domain mapping, ChIP, reporter assays, site-directed mutagenesis, SPR/MST binding, xenograft and disease models

    PMID:37415103 PMID:38574881 PMID:38858351 PMID:39510452 PMID:39706989 PMID:39890789 PMID:39923427

    Open questions at the time
    • Each regulator largely single-laboratory and context-specific
    • Integration of these inputs into one regulatory hierarchy unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the catalytic (Fe²⁺-liberating, pro-ferroptotic) and non-enzymatic (immune-suppressive, scaffold, mitochondrial) functions of HO-1 are switched within a single cell, and what determines the cytoprotective versus cytotoxic balance, remains unresolved.
  • No unified model of catalytic versus scaffold function
  • Determinants of context-dependent ferroptotic outcome undefined
  • Protease and signals controlling HO-1 cleavage/subcellular partitioning unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0016491 oxidoreductase activity 2 GO:0016787 hydrolase activity 1
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1430728 Metabolism 2 R-HSA-9612973 Autophagy 2
Partners
CGASIRF3LDHBPTGDSSIAH2STINGTRC8USP7

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 HO-1 (HMOX1) is an inducible 32-kDa microsomal enzyme that catalyzes the regiospecific oxidative catabolism of heme, producing equimolar amounts of carbon monoxide (CO), ferrous iron (Fe²⁺), and biliverdin. A constitutive isoform HO-2 (36 kDa) also exists but is unresponsive to HO-1 inducers. Biochemical characterization, pharmacological inhibitor studies Current medicinal chemistry High 23746277
2009 In myeloid cells, HO-1 forms a protein complex with the transcription factor IRF3 and is required for IRF3 phosphorylation and subsequent type-I interferon and chemokine gene induction (TLR3/TLR4/RIG-I pathway). Myeloid HO-1-deficient mice show reduced expression of IRF3 target genes, revealing a non-enzymatic, scaffold-like function of HO-1 in innate immune signaling. Co-immunoprecipitation (complex formation), myeloid-specific HO-1 knockout mice, gene expression analysis Advances in experimental medicine and biology Medium 21842368
2017 Cardiomyocyte-specific Hmox1 knockout (HO-1[CM]-/-) mice exposed to oxidative stress (hyperoxia) showed suppression of the Pgc-1α/NRF-1 axis, impaired LC3II processing, failure to upregulate Pink1- and Park2-mediated mitophagy, mitochondrial swelling, cardiomyocyte death, and cardiomyopathy. HO-1 thus regulates genetic programs for mitochondrial quality control (autophagy/mitophagy) downstream of NRF-1 binding to Pink1 and Park2 promoters. Conditional cardiomyocyte-specific Hmox1 knockout mice, electron microscopy, LC3II/p62 immunoblotting, NRF-1 promoter binding analysis JCI insight High 28194437
2019 Astrocyte-specific overexpression of human HMOX1 (GFAP.HMOX1 transgenic mice) promotes α-synuclein overproduction by downmodulating miR-153 and miR-223, two microRNAs that negatively regulate α-synuclein. Co-culture of wild-type neurons with GFAP.HMOX1 astrocytes caused enhanced protein oxidation, mitophagy, apoptosis, and dopaminergic gene dysregulation; siRNA knockdown of α-synuclein partially abrogated these effects. Transgenic mouse model, miRNA profiling, siRNA knockdown, neuron-astrocyte co-culture, Western blot, gene expression analysis Glia Medium 31180611
2019 Glial astrocytic HO-1 up-regulation causes accumulation of non-transferrin iron in the mitochondrial compartment, promotes intracellular oxidative stress, opening of the mitochondrial permeability transition pore, and renders co-cultured neuron-like PC12 cells prone to oxidative injury. Transient transfection overexpression of HO-1 in astrocytes, mitochondrial iron measurement, mitochondrial permeability transition assay, co-culture neurotoxicity assay Current Alzheimer research Medium 19874266
2015 Progesterone acts as an upstream modulator of placental Hmox1 expression; gestational stress reduces progesterone levels and increases methylation at distinct regions of the Hmox1 promoter, decreasing Hmox1 expression. Hmox1-deficient mice show reduced CD8+CD122+ tolerogenic T cells, and Hmox1 deficiency worsens fetal-growth restriction, placing HO-1 downstream of progesterone in regulating CD8+ T cell tolerance at the maternal-fetal interface. Progesterone receptor-deficient mice, Hmox1-deficient mice, promoter methylation analysis, CD8+ T cell depletion, progesterone supplementation rescue The Journal of clinical investigation High 25774501
2022 The deubiquitinase USP7 directly binds HO-1 and promotes its deubiquitination and stabilization after oxidative stress (arsenic exposure). HO-1 protein is ubiquitinated at K243 under resting conditions, leading to proteasomal degradation. Upon arsenic exposure, USP7 is itself ubiquitinated at K476, enhancing USP7–HO-1 interaction and HO-1 protein accumulation, thereby attenuating oxidative damage. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K243, K476), USP7 depletion, in vivo tumor growth assay, correlation in human HCC specimens Oncogene High 35821281
2023 USP7 directly binds to HMOX-1, and USP7 overexpression promotes HMOX-1 expression via deubiquitination in a spinal cord injury (SCI) rat model, thereby reducing ferroptosis and alleviating spinal cord damage. Co-immunoprecipitation, ubiquitination level measurement after USP7 overexpression, in vivo SCI rat model with locomotor scoring and histology Neurochemistry international Medium 37257587
2020 SIAH2, a RING-domain ubiquitin E3 ligase, mediates proteasome-dependent degradation of HO-1 through direct interaction with HO-1. SIAH2 knockout mice and human cells deleted for SIAH2 show elevated HO-1 protein levels in specific organs (heart, kidney, skeletal muscle), explained both by increased protein stability (SIAH2-HO-1 interaction) and by elevated HMOX1 transcription via NRF2 (itself a SIAH2 target). SIAH2 knockout mice, SIAH2 CRISPR knockout human cells, co-immunoprecipitation, proteasome inhibitor experiments, RING domain-dependent interaction assay Scientific reports High 32042051
2024 Full-length ER-anchored HO-1 disrupts STING polymerization and subsequent COPII-mediated ER-to-Golgi transport, suppressing downstream IFN signaling. Additionally, radiation-induced cleavage of HO-1 generates a fragment that undergoes nuclear translocation, where it interacts with cGAS and inhibits its nuclear export, suppressing cGAMP production and type-I IFN induction. HO-1 thus comprehensively inhibits the cGAS/STING pathway. Unbiased CRISPR screen, biochemical STING polymerization assay, COPII transport assay, nuclear fractionation showing cleaved HO-1 nuclear localization, cGAS co-immunoprecipitation, cGAMP measurement, in vivo tumor radiotherapy with HO-1 inhibitors The Journal of clinical investigation High 39621310
2024 HMOX1 interacts directly with lactate dehydrogenase B (LDHB) in foamy macrophages; this interaction enables the mitochondrial protease LONP1 to degrade mitochondrial transcription factor A (TFAM), causing mitochondrial dysfunction and sensitizing cells to ferroptosis. This mechanism operates specifically in TREM2-low foamy macrophages with low oxidative phosphorylation. Single-cell and bulk RNA sequencing, Co-immunoprecipitation (HMOX1-LDHB interaction), LONP1 inhibitor (bortezomib) rescue, MitoTEMPO treatment, mouse atherosclerosis model Developmental cell High 39731912
2023 The lncRNA RGMB-AS1 interacts with HO-1 (HMOX1) protein and prevents its ubiquitination by the E3 ligase TRC8, thereby stabilizing HMOX1 protein and promoting ferroptosis in NSCLC cells. RGMB-AS1 also independently binds to NAA10 (residues 82–87) to stimulate its acetyltransferase activity. Co-immunoprecipitation (RGMB-AS1–HMOX1 interaction), TRC8 ubiquitination assay, domain mapping (NAA10 residues 82–87), siRNA knockdown, in vivo xenograft model Cancer letters Medium 38574881
2018 Heat shock factor 4 (HSF4) directly binds to the heat shock element (HSE) in the HMOX1 promoter (at -389 to -362 bp upstream of the TSS) to activate HMOX1 transcription in human lens epithelial cells. HSF4 siRNA knockdown inhibits HMOX1 expression. Luciferase reporter assay, promoter deletion/mutation mapping, siRNA knockdown, Western blot and qPCR Gene Medium 29454088
2010 EGR-1 (early growth response 1) transcription factor regulates HO-1 expression induced by cigarette smoke. EGR-1 undergoes nuclear localization in lung fibroblasts after CSE exposure, and an EGR-1 binding site in the HO-1 enhancer region is responsible for induction. Egr-1-deficient MEFs show decreased CSE-induced HO-1 expression, and CS-exposed EGR-1 loss-of-function mice show exaggerated lung injury. Luciferase reporter assay with EGR-1 binding site, Egr-1 knockout MEFs, nuclear localization imaging, in vivo CS exposure model Biochemical and biophysical research communications Medium 20417178
2011 Nrf2 is required for CsA-stimulated HO-1 mRNA expression in human gingival fibroblasts. ERK kinase inhibition reduces CsA-stimulated Nrf2 nuclear translocation and HO-1 mRNA expression. NF-κB inhibition has no effect on CsA-stimulated HO-1, establishing Nrf2 (not NF-κB) as the mediator of CsA-induced HO-1 expression via ERK signaling. siRNA knockdown of Nrf2, NF-κB inhibitor, ERK kinase inhibitor, nuclear translocation assay, RT-PCR Journal of dental research Medium 21622902
2009 Iron-mediated upregulation of HMOX1 in hepatoma cells expressing HCV operates through the Nrf2 pathway: Nrf2 siRNA knockdown decreases FeNTA-mediated HMOX1 mRNA upregulation. Iron does not affect Bach1 (a repressor of HMOX1) mRNA or protein levels, distinguishing iron-Nrf2 from iron-Bach1 mechanisms in this context. Nrf2 siRNA knockdown, Western blot, qRT-PCR, deferoxamine inhibition World journal of gastroenterology Medium 19777608
2023 HMOX1 promotes ferroptosis by catalyzing heme degradation to release Fe²⁺ (ferrous iron). In human lens epithelial cells (HLECs) and cisplatin-resistant ovarian cancer cells, forced HMOX1 overexpression increases intracellular Fe²⁺ and lipid peroxidation and sensitizes cells to ferroptosis, while HMOX1 knockout/knockdown reduces Fe²⁺ and attenuates ferroptosis. This identifies HMOX1 as a pro-ferroptotic enzyme through its iron-liberating catalytic activity. CRISPR-Cas9 HMOX1 knockout, lentiviral overexpression, siRNA knockdown, ferrous/ferric iron measurement, lipid peroxidation assay (MDA), cell viability Current eye research; Phytomedicine High 36300537 36773431
2024 P300 (histone acetyltransferase) normally interacts with HIF-1α to suppress HMOX1 expression. When P300 expression is reduced by ferroptosis inducers, HIF-1α preferentially binds P53 instead, driving HMOX1 overexpression and promoting VSMC ferroptosis. Co-immunoprecipitation confirmed competitive binding of P300 and P53 to HIF-1α. Co-immunoprecipitation (P300–HIF-1α and HIF-1α–P53 interactions), shRNA knockdown, specific inhibitor A-485, HIF-1α inhibitor BAY87-2243 rescue, lipid peroxidation assay Molecular medicine Medium 37415103
2023 Ythdf2 (an m6A reader protein) promotes degradation of Hmox1 mRNA in an m6A-dependent manner in alveolar macrophages. Myeloid-specific Ythdf2 knockout results in elevated Hmox1 mRNA and protein, attenuated macrophage polarization and oxidative stress, and protection from pulmonary hypertension. Pharmacological inhibition of Hmox1 reversed the protective phenotype of Ythdf2 knockout mice. Myeloid-specific Ythdf2 knockout mice, m6A-dependent mRNA stability assay, Hmox1 inhibitor rescue, right ventricular hypertrophy and pulmonary vascular remodeling readouts Redox biology Medium 36801705
2024 The histone acetyltransferase Kat2a promotes ferroptosis in diabetic cardiomyopathy by increasing H3K27ac and H3K9ac enrichment on the promoter regions of Tfrc and Hmox1, thereby enhancing their transcription. This Kat2a-driven upregulation of Hmox1 (and Tfrc) increases iron availability and promotes ferroptosis. ChIP assay (H3K27ac and H3K9ac enrichment on Hmox1 promoter), Kat2a inhibition/overexpression, in vitro high-glucose cardiomyocyte model, in vivo DCM model Cell death & disease Medium 38858351
2018 Scavenging of hemoglobin:haptoglobin complexes via CD163 receptor on macrophages leads to nuclear translocation of Nrf2, upregulation of HO-1, and release of IL-10. This CD163-Nrf2-HO-1-IL-10 axis mediates M1-to-M2 macrophage switching, and IL-10 feeds back to further upregulate CD163. Macrophage receptor (CD163) signaling experiments, Nrf2 nuclear translocation assay, hemin activation in rodent diabetes models, Hp2 polymorphism association studies Current pharmaceutical design Medium 30014796
2018 Mkp-1 (mitogen-activated protein kinase phosphatase 1) directly interacts with the DIDLID motif of Nrf2, increasing Nrf2 stability and positively regulating HO-1 expression. Conversely, Nrf2 activates Mkp-1 transcription via antioxidant response elements (AREs) in the Mkp-1 promoter. Mkp-1-/- mice show increased susceptibility to DSS-induced colitis. Co-immunoprecipitation (Mkp-1–Nrf2 DIDLID motif interaction), Mkp-1 knockout mice, ARE-driven luciferase reporter assay, siRNA, Western blot Free radical biology & medicine Medium 30061089
2021 HO-1 induction in cardiomyocytes during hypoxia/reoxygenation (H/R) injury promotes autophagy (increased LC3II, decreased p62) and protects mitochondrial membrane potential and reduces mitochondrial ROS. HO-1 overexpression (Lv-HO1-H9c2 cell line) enhances autophagic flux, while HO-1 inhibition with ZnPP suppresses autophagy and worsens mitochondrial dysfunction. Lentiviral HO-1 overexpression, HO-1 inhibitor (ZnPP), LC3II/p62 Western blot, RFP-GFP-LC3 double-label adenovirus confocal microscopy, JC-1 mitochondrial membrane potential assay, flow cytometry PloS one Medium 27138700
2024 PTGDS (prostaglandin D2 synthase) interacts with HMOX1 protein, and targeting PTGDS increases intracellular iron levels and induces ferroptosis through promoting HMOX1-mediated heme catabolism and ferritin autophagy. An H25A mutation in HMOX1 was identified as the key functional residue for this PTGDS-dependent ferroptotic role. Co-immunoprecipitation (PTGDS–HMOX1), TMT mass spectrometry, RNA-seq, site-directed mutagenesis (H25A), lentiviral gene silencing, xenograft model British journal of cancer Medium 39706989
2016 Nrf2 binds to ARE sequences in the promoter regions of HO-1 (HMOX1), GCLM, and x-CT target genes in neuroblastoma cells treated with bortezomib, driving their transcription. HO-1 silencing combined with GSH depletion synergistically decreases cell viability in bortezomib-treated cells, demonstrating that HO-1 contributes to Nrf2-mediated chemoresistance. Nrf2 ChIP/ARE binding assay, HO-1 siRNA silencing, pharmacological GSH depletion, cell viability assay PloS one Medium 27023064
2024 IFI16 activates HMOX1 transcription by interacting with the transcription factors JUND and SP1 through its pyrin domain, thereby robustly facilitating HMOX1 expression. Elevated HMOX1 attenuates ferroptosis (reduced lipid peroxidation, ROS, and Fe²⁺) after irradiation, enhancing radioresistance in glioblastoma. The compound glyburide disrupts IFI16 function and reduces HMOX1 expression, restoring radiosensitivity. Co-immunoprecipitation (IFI16–JUND, IFI16–SP1 via pyrin domain), CRISPR/IFI16 manipulation, HMOX1 reporter/ChIP, radioresistant GBM cell model, ferroptosis assays Nature communications High 39890789
2025 FOSL1 (a transcription factor) transcriptionally activates HMOX1 by binding to its promoter. Juglone increases FOSL1 and HMOX1 expression, driving ferroptosis in HCC cells; HMOX1 silencing attenuates juglone-induced ferroptosis. Dual-luciferase reporter assay identified the specific FOSL1 binding site in the HMOX1 promoter. Dual-luciferase reporter assay with HMOX1 promoter, gene silencing (HMOX1 siRNA), RNA-seq and proteomics, xenograft model Phytomedicine Medium 39923427
2004 Prolactin (PRL) increases HO-1 expression and protein synthesis in human macrophages in a time- and dose-dependent manner, and PRL-treated macrophages show enhanced VEGF release. HO-1 activity is required for PRL-induced VEGF production, as demonstrated using the HO inducer SnCl₂ and the HO inhibitor SnMP. RT-real-time PCR, Western blot, ELISA for VEGF, pharmacological HO-1 inducer (SnCl₂) and inhibitor (SnMP) experiments Journal of cellular biochemistry Medium 15352176
2015 HO-1 induction in microglia (not astrocytes) mediates curcumin's glioprotective and anti-inflammatory effects. Glial cultures from LysM(Cre) Hmox(Δ/Δ) microglial-specific HO-1 knockout mice lose curcumin's protective effect. HO-1 inhibitor SnPP blocks curcumin-afforded ROS reduction and cell protection, and HO-1 promotes microglial ramified anti-inflammatory morphology in an HO-1-dependent manner. Myeloid-specific HO-1 conditional knockout (LysM(Cre) Hmox(Δ/Δ)), SnPP HO-1 inhibitor, primary glial cultures, morphological analysis, cytokine measurement Molecular nutrition & food research Medium 26047311
2021 HO-1 induction in prostate cancer cells (PC3, C4-2B) with hemin impairs cellular metabolic rate, reducing glucose uptake, ATP production, LDH activity, and extracellular lactate, indicating HO-1 modulates aerobic glycolysis through lactate dehydrogenase (LDH). Pharmacological HO-1 induction (hemin), glucose uptake assay, ATP measurement, LDH activity assay, lactate measurement Antioxidants (Basel, Switzerland) Low 34208670
2024 Ginsenoside Rb1 specifically targets HO-1 protein at the K18A residue, as determined by molecular docking, surface plasmon resonance (SPR), and microscale thermophoresis (MST). Rb1 reduces HO-1 expression, inhibits ferroptosis in sepsis-induced organ tissues, and improves sepsis outcomes in vivo. Molecular docking, surface plasmon resonance, microscale thermophoresis (direct binding assays), HO-1 inhibitor (ZNPP), CLP mouse model, in vitro LPS/THP-1 Free radical biology & medicine Medium 39510452
2021 HMOX1 knockdown in human endothelial cells attenuates Fe²⁺ overload, reduces iron content and ROS, alleviates lipid peroxidation, and reduces ferroptosis in a diabetic high-glucose/high-lipid context, demonstrating that HMOX1 upregulation is causally responsible for increased ferroptosis in diabetic atherosclerosis. siRNA knockdown of HMOX1, ferrostatin-1 ferroptosis inhibitor, Fe²⁺ iron content measurement, ROS detection, lipid peroxidation assay Life sciences Medium 34508760

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1. Acta pharmaceutica Sinica. B 282 35646542
2015 The Nrf2/HO-1 Axis in Cancer Cell Growth and Chemoresistance. Oxidative medicine and cellular longevity 244 26697129
2017 HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation. Antioxidants (Basel, Switzerland) 185 28475131
2021 HMOX1 upregulation promotes ferroptosis in diabetic atherosclerosis. Life sciences 162 34508760
2023 Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation. Phytomedicine : international journal of phytotherapy and phytopharmacology 131 36773431
2024 The Nrf2-HO-1 system and inflammaging. Frontiers in immunology 122 39380993
2023 Donafenib and GSK-J4 Synergistically Induce Ferroptosis in Liver Cancer by Upregulating HMOX1 Expression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 119 37330650
2022 6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway. Oxidative medicine and cellular longevity 112 36624878
2018 M1/M2 Macrophages in Diabetic Nephropathy: Nrf2/HO-1 as Therapeutic Targets. Current pharmaceutical design 89 30014796
2009 Immunoregulatory effects of HO-1: how does it work? Current opinion in pharmacology 84 19586801
2017 Mitochondrial quality-control dysregulation in conditional HO-1-/- mice. JCI insight 74 28194437
2022 Identification of HMOX1 as a Critical Ferroptosis-Related Gene in Atherosclerosis. Frontiers in cardiovascular medicine 71 35498043
2022 Flavonoid 4,4'-dimethoxychalcone induced ferroptosis in cancer cells by synergistically activating Keap1/Nrf2/HMOX1 pathway and inhibiting FECH. Free radical biology & medicine 71 35697292
2015 Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation. The Journal of clinical investigation 69 25774501
2023 Sirtuin4 alleviates severe acute pancreatitis by regulating HIF-1α/HO-1 mediated ferroptosis. Cell death & disease 66 37865653
2015 Microglial HO-1 induction by curcumin provides antioxidant, antineuroinflammatory, and glioprotective effects. Molecular nutrition & food research 66 26047311
2013 A focus on heme oxygenase-1 (HO-1) inhibitors. Current medicinal chemistry 65 23746277
2018 Mkp-1 cross-talks with Nrf2/Ho-1 pathway protecting against intestinal inflammation. Free radical biology & medicine 58 30061089
2009 Suppression of glial HO-1 activity as a potential neurotherapeutic intervention in AD. Current Alzheimer research 55 19874266
2023 Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells. Chinese medical journal 51 37488674
2023 Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression. Oxidative medicine and cellular longevity 49 36691638
2019 Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation. Scientific reports 48 31239473
2023 Ythdf2 promotes pulmonary hypertension by suppressing Hmox1-dependent anti-inflammatory and antioxidant function in alveolar macrophages. Redox biology 47 36801705
2023 Histone acetyltransferase P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/HMOX1 axis. Molecular medicine (Cambridge, Mass.) 45 37415103
2016 Role of Nrf2, HO-1 and GSH in Neuroblastoma Cell Resistance to Bortezomib. PloS one 45 27023064
2015 The role of HO-1 in protection against lead-induced neurotoxicity. Neurotoxicology 43 26542248
2024 HMOX1-LDHB interaction promotes ferroptosis by inducing mitochondrial dysfunction in foamy macrophages during advanced atherosclerosis. Developmental cell 42 39731912
2016 TGFβ-Responsive HMOX1 Expression Is Associated with Stemness and Invasion in Glioblastoma Multiforme. Stem cells (Dayton, Ohio) 42 27354342
2024 LncRNA RGMB-AS1 inhibits HMOX1 ubiquitination and NAA10 activation to induce ferroptosis in non-small cell lung cancer. Cancer letters 41 38574881
2018 HO-1hi patrolling monocytes protect against vaso-occlusion in sickle cell disease. Blood 41 29437594
2023 Modulation of Nrf2/HO-1 by Natural Compounds in Lung Cancer. Antioxidants (Basel, Switzerland) 40 36978983
2023 Nrf2/HO-1 as a therapeutic target in renal fibrosis. Life sciences 40 37890696
2024 Histone acetyltransferase Kat2a regulates ferroptosis via enhancing Tfrc and Hmox1 expression in diabetic cardiomyopathy. Cell death & disease 38 38858351
2022 Maackiain protects against sepsis via activating AMPK/Nrf2/HO-1 pathway. International immunopharmacology 38 35405595
2022 Baicalin improved hepatic injury of NASH by regulating NRF2/HO-1/NRLP3 pathway. European journal of pharmacology 38 36184988
2021 Association between HO‑1 gene promoter polymorphisms and diseases (Review). Molecular medicine reports 36 34841438
2025 Cellular senescence-associated gene IFI16 promotes HMOX1-dependent evasion of ferroptosis and radioresistance in glioblastoma. Nature communications 35 39890789
2023 USP7 regulates HMOX-1 via deubiquitination to suppress ferroptosis and ameliorate spinal cord injury in rats. Neurochemistry international 34 37257587
2021 HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis. Frontiers in cell and developmental biology 34 34917622
2019 The role of TLR4 and HO-1 in neuroinflammation after subarachnoid hemorrhage. Journal of neuroscience research 34 31468571
2004 Prolactin increases HO-1 expression and induces VEGF production in human macrophages. Journal of cellular biochemistry 34 15352176
2023 Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer. BMC pulmonary medicine 32 37749553
2016 HO-1 Protects against Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction in H9c2 Cardiomyocytes. PloS one 31 27138700
2009 Iron increases HMOX1 and decreases hepatitis C viral expression in HCV-expressing cells. World journal of gastroenterology 31 19777608
2021 Nattokinase Attenuates Retinal Neovascularization Via Modulation of Nrf2/HO-1 and Glial Activation. Investigative ophthalmology & visual science 29 34036312
2024 Effective protective mechanisms of HO-1 in diabetic complications: a narrative review. Cell death discovery 28 39389941
2022 Hemin mitigates contrast-induced nephropathy by inhibiting ferroptosis via HO-1/Nrf2/GPX4 pathway. Clinical and experimental pharmacology & physiology 28 35598290
2020 Glycine Improves Ischemic Stroke Through miR-19a-3p/AMPK/GSK-3β/HO-1 Pathway. Drug design, development and therapy 28 32546967
2022 The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1. Oncogene 27 35821281
2023 Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway. International journal of immunopathology and pharmacology 26 38031977
2022 Stevioside attenuates osteoarthritis via regulating Nrf2/HO-1/NF-κB pathway. Journal of orthopaedic translation 26 36439628
2011 A new role for myeloid HO-1 in the innate to adaptive crosstalk and immune homeostasis. Advances in experimental medicine and biology 26 21842368
2019 Glial HMOX1 expression promotes central and peripheral α-synuclein dysregulation and pathogenicity in parkinsonian mice. Glia 25 31180611
2018 Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway. Oxidative medicine and cellular longevity 25 29765498
2024 Upregulation of HMOX1 associated with M2 macrophage infiltration and ferroptosis in proliferative diabetic retinopathy. International immunopharmacology 23 38739977
2021 Contributions of HO-1-Dependent MAPK to Regulating Intestinal Barrier Disruption. Biomolecules & therapeutics 23 33093265
2020 SIAH2-mediated and organ-specific restriction of HO-1 expression by a dual mechanism. Scientific reports 22 32042051
2021 HO-1: A new potential therapeutic target to combat osteoporosis. European journal of pharmacology 20 34081904
2017 Generation of CMAHKO/GTKO/shTNFRI-Fc/HO-1 quadruple gene modified pigs. Transgenic research 20 28553699
2024 Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway. Molecules (Basel, Switzerland) 19 38930897
2023 Zoledronic acid induces ferroptosis by reducing ubiquinone and promoting HMOX1 expression in osteosarcoma cells. Frontiers in pharmacology 19 36686696
2022 Menthae Herba Attenuates Neuroinflammation by Regulating CREB/Nrf2/HO-1 Pathway in BV2 Microglial Cells. Antioxidants (Basel, Switzerland) 19 35453334
2022 Role of Nrf2 and HO-1 in intervertebral disc degeneration. Connective tissue research 19 35736364
2021 HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth. Cells 19 34359970
2019 HO-1 and CD39: It Takes Two to Protect the Realm. Frontiers in immunology 19 31402920
2010 EGR-1 regulates Ho-1 expression induced by cigarette smoke. Biochemical and biophysical research communications 19 20417178
2025 Elevated Histone Lactylation Mediates Ferroptosis Resistance in Endometriosis Through the METTL3-Regulated HIF1A/HMOX1 Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 40492577
2024 SEH1L siliencing induces ferroptosis and suppresses hepatocellular carcinoma progression via ATF3/HMOX1/GPX4 axis. Apoptosis : an international journal on programmed cell death 18 39095556
2024 HO-1 impairs the efficacy of radiotherapy by redistributing cGAS and STING in tumors. The Journal of clinical investigation 18 39621310
2023 Ferrostatin-1 Blunts Right Ventricular Hypertrophy and Dysfunction in Pulmonary Arterial Hypertension by Suppressing the HMOX1/GSH Signaling. Journal of cardiovascular translational research 18 37603208
2021 HO-1 Modulates Aerobic Glycolysis through LDH in Prostate Cancer Cells. Antioxidants (Basel, Switzerland) 18 34208670
2022 Urolithin A ameliorates diabetic retinopathy via activation of the Nrf2/HO-1 pathway. Endocrine journal 17 35321989
2019 Role of Nrf2/HO-1 and PI3K/Akt Genes in the Hepatoprotective Effect of Cilostazol. Current clinical pharmacology 17 30179140
2011 Nrf-2 regulates cyclosporine-stimulated HO-1 expression in gingiva. Journal of dental research 17 21622902
2024 DDIT3 aggravates TMJOA cartilage degradation via Nrf2/HO-1/NLRP3-mediated autophagy. Osteoarthritis and cartilage 16 38719085
2024 Ginsenoside Rb1 targets to HO-1 to improve sepsis by inhibiting ferroptosis. Free radical biology & medicine 16 39510452
2023 HMOX1 pathway signature predicts clinical benefit from immunotherapy plus tyrosine kinase inhibitor therapy in advanced renal cell carcinoma. Cancer medicine 16 37031459
2022 HMOX1 Promotes Ferroptosis Induced by Erastin in Lens Epithelial Cell through Modulates Fe2+ Production. Current eye research 16 36300537
2019 Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression. Biochemical and biophysical research communications 16 31813548
2006 No nitric oxide for HO-1 from sodium nitroprusside. Molecular pharmacology 16 16476785
2024 HO-1-mediated ferroptosis regulates retinal neovascularization via the COX2/VEGFA axis. Free radical biology & medicine 15 39542186
2023 Koumine ameliorates neuroinflammation by regulating microglia polarization via activation of Nrf2/HO-1 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 37801902
2023 HMOX1-overexpressing mesenchymal stem cell-derived exosomes facilitate diabetic wound healing by promoting angiogenesis and fibroblast function. Biochemical and biophysical research communications 15 38006802
2022 MicroRNA-122-5p regulates coagulation and inflammation through MASP1 and HO-1 genes. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 15 35293311
2024 Novel methyltransferase G9a inhibitor induces ferroptosis in multiple myeloma through Nrf2/HO-1 pathway. Annals of hematology 14 38538975
2023 Valuable effects of lactobacillus and citicoline on steatohepatitis: role of Nrf2/HO-1 and gut microbiota. AMB Express 14 37291355
2025 HMOX1 as a potential drug target for upper and lower airway diseases: insights from multi-omics analysis. Respiratory research 13 39871287
2024 EGR1 Promotes Erastin-induced Ferroptosis Through Activating Nrf2-HMOX1 Signaling Pathway in Breast Cancer Cells. Journal of Cancer 13 39006084
2024 Targeting PTGDS Promotes ferroptosis in peripheral T cell lymphoma through regulating HMOX1-mediated iron metabolism. British journal of cancer 13 39706989
2022 Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats. Open life sciences 13 35434371
2022 HMOX1 silencing prevents doxorubicin-induced cardiomyocyte injury, mitochondrial dysfunction, and ferroptosis by downregulating CTGF. General thoracic and cardiovascular surgery 13 36008747
2025 Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis. Bone research 12 39814705
2025 Juglone induces ferroptotic effect on hepatocellular carcinoma and pan-cancer via the FOSL1-HMOX1 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 12 39923427
2025 Targeting the proliferation of glioblastoma cells and enhancement of doxorubicin and temozolomide cytotoxicity through inhibition of PFKFB4 and HMOX1 genes with siRNAs. Scientific reports 12 40739397
2024 Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway. Drug design, development and therapy 12 39741916
2022 HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review. PloS one 12 35551540
2021 Hyperhomocysteinemia-induced Nrf2/HO-1 pathway suppression aggravates cardiac remodeling of hypertensive rats. Biochemical and biophysical research communications 12 33610040
2018 HSF4 transcriptional regulates HMOX-1 expression in HLECs. Gene 12 29454088
2014 P8 deficiency increases cellular ROS and induces HO-1. Archives of biochemistry and biophysics 12 25475530
2015 HO-1 expression control in the rat glomerulus. Biochemical and biophysical research communications 11 25824035

Missed literature

Know a paper Affinage missed for HMOX1? Flag it for the maintainers and the community.

No submissions yet.