ReviewFrontiers in medicine2026
Current research on the HIF-2α-EPO-Hb axis in hypoxic environments: from molecular mechanisms to clinical.
Review in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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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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.
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Who cites it
2 citing papers in PubMed.
- The Lung-Kidney Axis: A Coordinated Regulation of Oxygen Sensing and Erythropoiesis.Biomedicines · 2026Review
- Incidence and risk factors of acute kidney injury among neurocritical patients in high-altitude regions: a retrospective cohort study.Frontiers in medicine · 2026Article
Corrections and comments
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Authors and funding
3 authors.
Funding
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Abstract
Hypoxic environments modulate downstream gene expression via activation of the hypoxia-inducible factor (HIF) signaling pathway, which facilitates adaptive responses to low oxygen. Under hypoxic conditions, HIF-2α is stabilized and translocated to the nucleus, where it binds to hypoxia-response elements and upregulates transcription of the erythropoietin (EPO) gene. Increased EPO stimulates red blood cell production in the bone marrow, raising hemoglobin (Hb) levels to improve oxygen transport. This review examines the principal regulatory pathway, the Hypoxia-Inducible Factor-2α-Erythropoietin-Hemoglobin axis (HIF-2α-EPO-Hb), which governs physiological and pathological responses to hypoxia. The HIF-2α-EPO-Hb axis dynamically regulates erythropoietin and hemoglobin production in response to fluctuations in oxygen levels, maintaining systemic oxygen homeostasis. This pathway is involved in both physiological processes, such as high-altitude adaptation, and pathological conditions. Disruption of this axis leads to anemia associated with chronic kidney disease, while excessive activation contributes to high-altitude polycythemia and tumor progression, including renal cell carcinoma. The complex regulatory networks of this axis across diverse tissue microenvironments and disease states remain incompletely characterized. Targeted interventions, such as hypoxia-inducible factor-prolyl hydroxylase inhibitors and hypoxia-inducible factor-2α inhibitors, face significant challenges in tissue selectivity, long-term safety, and efficacy prediction. This review elucidates the molecular regulatory mechanisms of the HIF-2α-EPO-Hb axis, delineates its dysregulation in chronic hypoxic diseases and tumorigenesis, and evaluates current research progress and clinical limitations of related therapies. The discussion provides theoretical foundations and future perspectives for mechanistic research and clinical intervention in relevant diseases.
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