ArticleScientific reports2016
Role Of Hif2α Oxygen Sensing Pathway In Bronchial Epithelial Club Cell Proliferation.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models.Science translational medicine · 2025Article
- Influence of Hypoxia on the Airway Epithelium.Physiological research · 2024Review
- Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type-Specific and Time-Resolved Responses to Vhl Inactivation in the Kidney.Cancer research · 2024Article
- Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes?European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Molecular and Functional Characteristics of Airway Epithelium under Chronic Hypoxia.International journal of molecular sciences · 2023Article
- Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders.Frontiers in physiology · 2023Article
- HIF-1α is essential for the augmentation of myometrial contractility during labor†.Biology of reproduction · 2022Article
- Hypoxia induces adrenomedullin from lung epithelia, stimulating ILC2 inflammation and immunity.The Journal of experimental medicine · 2022Article
- Review
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- Macrophage-Regulatory T Cell Interactions Promote Type 2 Immune Homeostasis Through Resistin-Like Molecule α.Frontiers in immunology · 2021Article
- Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis.Frontiers in pharmacology · 2021Article
- Cobalt chloride-stimulated hypoxia promotes the proliferation of cholesteatoma keratinocytes via the PI3K/Akt signaling pathway.International journal of medical sciences · 2021Article
- Endothelial Oxygen Sensing in Alveolar Maintenance.American journal of respiratory and critical care medicine · 2020Article
- Hypoxia-inducible factor 2α drives hepatosteatosis through the fatty acid translocase CD36.Liver international : official journal of the International Association for the Study of the Liver · 2020Article
- Consecutive Hypoxia Decreases Expression ofFrontiers in cell and developmental biology · 2020Article
- FoxM1 is regulated by both HIF-1α and HIF-2α and contributes to gastrointestinal stromal tumor progression.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxygen-sensing pathways executed by the hypoxia-inducible factors (HIFs) induce a cellular adaptive program when oxygen supply becomes limited. However, the role of the HIF oxygen-sensing pathway in the airway response to hypoxic stress in adulthood remains poorly understood. Here we found that in vivo exposure to hypoxia led to a profound increase in bronchial epithelial cell proliferation mainly confined to Club (Clara) cells. Interestingly, this response was executed by hypoxia-inducible factor 2α (HIF2α), which controls the expression of FoxM1, a recognized proliferative factor of Club cells. Furthermore, HIF2α induced the expression of the resistin-like molecules α and β (RELMα and β), previously considered bronchial epithelial growth factors. Importantly, despite the central role of HIF2α, this proliferative response was not initiated by in vivo Vhl gene inactivation or pharmacological inhibition of prolyl hydroxylase oxygen sensors, indicating the molecular complexity of this response and the possible participation of other oxygen-sensing pathways. Club cells are principally involved in protection and maintenance of bronchial epithelium. Thus, our findings identify a novel molecular link between HIF2α and Club cell biology that can be regarded as a new HIF2α-dependent mechanism involved in bronchial epithelium adaptation to oxygen fluctuations.
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