ArticleThe Journal of clinical investigation2014
NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
70 citing papers in PubMed, 107 citations in OpenAlex.
- In Silico Perturbation Identifies Transcription Factors as Protective Targets in HSPCs After Irradiation.International journal of molecular sciences · 2026Article
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- An Update on Role of Ionizing Radiation to Enhance Proliferation and Differentiation of Normal Stem Cells via Activation of NRF2 Pathway: Review.Antioxidants (Basel, Switzerland) · 2025Review
- Single-cell transcriptomics reveals BMP4-BMPR2 signaling promotes radiation resistance in hematopoietic stem cells following injury.Nature communications · 2025Article
- Regio- and Stereoselective Synthesis of Nitro-fatty Acids as NRF2 Pathway Activators Working under Ambient or Hypoxic Conditions.Journal of medicinal chemistry · 2025Article
- Neural stem cells fate under neuroinflammatory conditions and oxidative stress response.Frontiers in cellular neuroscience · 2025Review
- NRF2 in age-related musculoskeletal diseases: Role and treatment prospects.Genes & diseases · 2024Review
- Role of ferroptosis in radiation-induced soft tissue injury.Cell death discovery · 2024Review
- Review
- Progression of Notch signaling regulation of B cells under radiation exposure.Frontiers in immunology · 2024Review
- Zinc Finger 521 Modulates the Nrf2-Notch Signaling Pathway in Human Ovarian Carcinoma.International journal of molecular sciences · 2023Article
- Prediction of hub genes and key pathways associated with the radiation response of human hematopoietic stem/progenitor cells using integrated bioinformatics methods.Scientific reports · 2023Article
- The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.The Journal of clinical investigation · 2023Article
- Cell-intrinsic factors governing quiescence vis-à-vis activation of adult hematopoietic stem cells.Molecular and cellular biochemistry · 2023Review
- Emerging Role of NRF2 Signaling in Cancer Stem Cell Phenotype.Molecules and cells · 2023Review
- Clock in radiation oncology clinics: cost-free modality to alleviate treatment-related toxicity.Cancer biology & therapy · 2022Review
- Review
- NRF2 Mediates Cellular Resistance to Transformation, Radiation, and Inflammation in Mice.Antioxidants (Basel, Switzerland) · 2022Article
- Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments.Archives of pharmacal research · 2022Review
- Chlorogenic Acid, the Main Antioxidant in Coffee, Reduces Radiation-Induced Apoptosis and DNA Damage via NF-E2-Related Factor 2 (Nrf2) Activation in Hepatocellular Carcinoma.Oxidative medicine and cellular longevity · 2022Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
A nuclear disaster may result in exposure to potentially lethal doses of ionizing radiation (IR). Hematopoietic acute radiation syndrome (H-ARS) is characterized by severe myelosuppression, which increases the risk of infection, bleeding, and mortality. Here, we determined that activation of nuclear factor erythroid-2-related factor 2 (NRF2) signaling enhances hematopoietic stem progenitor cell (HSPC) function and mitigates IR-induced myelosuppression and mortality. Augmenting NRF2 signaling in mice, either by genetic deletion of the NRF2 inhibitor Keap1 or by pharmacological NRF2 activation with 2-trifluoromethyl-2'-methoxychalone (TMC), enhanced hematopoietic reconstitution following bone marrow transplantation (BMT). Strikingly, even 24 hours after lethal IR exposure, oral administration of TMC mitigated myelosuppression and mortality in mice. Furthermore, TMC administration to irradiated transgenic Notch reporter mice revealed activation of Notch signaling in HSPCs and enhanced HSPC expansion by increasing Jagged1 expression in BM stromal cells. Administration of a Notch inhibitor ablated the effects of TMC on hematopoietic reconstitution. Taken together, we identified a mechanism by which NRF2-mediated Notch signaling improves HSPC function and myelosuppression following IR exposure. Our data indicate that targeting this pathway may provide a countermeasure against the damaging effects of IR exposure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.