ArticleThe Journal of clinical investigation2010
Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 300 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
300 citing papers in PubMed, 1 synthesis or guideline pooled it, 446 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.EBioMedicine · 2018Trial
- Trial
- Excess Cholesterol Biosynthesis by Up-regulated HMGCS1 in Colorectal Cancer Cells Induced M2-like Tumor-Associated Macrophage Polarization via Extracellular Vesicles.Cancer research and treatment · 2026Article
- Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.Translational lung cancer research · 2026Review
- Modulation of Pepsin-Mediated Inflammatory Responses in Vocal Cord Epithelial Cells by Amprenavir.The Laryngoscope · 2026Article
- The pivotal role of macrophages in tumorigenesis and pioneering cancer immunotherapy across pre-clinical and clinical frontiers.Journal of cancer research and clinical oncology · 2026Review
- Neonatal monocyte iron metabolism and immunometabolic responses in sepsis: a comparative ex vivo investigation.Pediatric research · 2026Article
- Geometry-driven immunomodulation in 3D-printed bioceramics: Negative curvature promotes macrophage M2 polarization via Ras-MAPK/HIF-1α signaling for vascularized osteogenesis.Bioactive materials · 2026Article
- <p>Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)</p>.International journal of oncology · 2026Review
- Hypoxia-Inducible Factors in Rheumatoid Arthritis: Central Pathogenic Roles and Therapeutic Opportunities.Journal of inflammation research · 2026Review
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- A transcriptomic atlas of macrophage polarization induced by inflammatory and reparative cytokines reveals cytokine-specific and synergistic polarization programs.Frontiers in immunology · 2026Article
- MiRNAs: a call to arms that shapes the plasticity of tumor associated macrophages in breast cancer.Frontiers in immunology · 2026Review
- Therapeutic targeting of local metabolic dysfunction in secondary lymphedema: mechanisms and opportunities.Frontiers in physiology · 2026Review
- Macrophages in Colorectal Cancer: from Normal Mucosa to Distant Metastasis: Beyond the M1/M2 Paradigm.Journal of Cancer · 2026Review
- Iron Deficiency Impairs Muscle Stem Cell Proliferation and Skeletal Muscle Regeneration via HIF-2α Stabilization.Journal of cachexia, sarcopenia and muscle · 2025Article
- Role of oxygen sensing and hypoxia-inducible factors in orchestrating innate immune responses.Nature immunology · 2025Review
- Immunomodulatory Role of Propolis in Hypoxia and in the Tumor Microenvironment.Molecules (Basel, Switzerland) · 2025Review
- Hypoxia and Multilineage Communication in 3D Organoids for Human Disease Modeling.Biomimetics (Basel, Switzerland) · 2025Review
240 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 4 countries.
Funding
Abstract
Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1alpha and HIF-2alpha, and overexpression of HIF-2alpha in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2alpha during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1alpha versus HIF-2alpha must be elucidated. We demonstrate here that mice lacking HIF-2alpha in myeloid cells (Hif2aDelta/Delta mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2alpha directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. Hif2aDelta/Delta mice displayed reduced TAM infiltration in independent murine hepatocellular and colitis-associated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2alpha modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2alpha as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer.
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What OpenQuestion holds
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.