ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Identification of hypoxia-inducible factor HIF-1A as transcriptional regulator of the A2B adenosine receptor during acute lung injury.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 108 citations in OpenAlex.
- Identification of HIF1A as a therapeutic target during SARS-CoV-2-associated lung injury.JCI insight · 2025Trial
- The lung-muscle metabolic axis: a proposed mechanism for post-resection systemic frailty.Surgery today · 2026Review
- Altered HIF-1α, Netrin-1, and Netrin-4 Levels in Obstructive Sleep Apnea: Associations with Intermittent Hypoxia and Disease Severity.Medicina (Kaunas, Lithuania) · 2026Article
- Adenosine Signaling as a Central Integrative Network in Cellular Stress Responses and a Therapeutically Actionable Target in Human Disease.Biomolecules · 2026Review
- Role of oxygen sensing and hypoxia-inducible factors in orchestrating innate immune responses.Nature immunology · 2025Review
- Decoding fibrosis in nonresolvable COVID-19: a role for myeloid-specific HIF1A deletion.American journal of physiology. Cell physiology · 2025Article
- NUDT21 Regulates Macrophage Cytokine Responses via Alternative Polyadenylation in ARDS.Research square · 2025Article
- Damage response signaling by the extracellular adenosine pathway: control of infection outcome during host aging.mSphere · 2025Review
- Review
- APurinergic signalling · 2025Review
- Exploring the pharmacological mechanisms for alleviating OSA: Adenosine A2A receptor downregulation of the PI3K/Akt/HIF‑1 pathway (Review).Biomedical reports · 2025Review
- Progressive Deactivation of Hydroxylases Controls Hypoxia-Inducible Factor-1α-Coordinated Cellular Adaptation to Graded Hypoxia.Research (Washington, D.C.) · 2025Article
- Research status of the relationship between microecological imbalance and lung cancer.Frontiers in microbiology · 2025Review
- Targeting nanoparticles to lung cancer-derived A549 cells based on changes on interstitial stiffness in biomimetic models.iScience · 2024Article
- Genetic and epigenetic regulation of cortactin (CTTN) by inflammatory factors and mechanical stress in human lung endothelial cells.Bioscience reports · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS).Respiratory research · 2024Review
- Hypoxia-adenosine axis as therapeutic targets for acute respiratory distress syndrome.Frontiers in immunology · 2024Review
- Interplay of hypoxia-inducible factors and oxygen therapy in cardiovascular medicine.Nature reviews. Cardiology · 2023Review
- Transcriptional control of pancreatic cancer immunosuppression by metabolic enzyme CD73 in a tumor-autonomous and -autocrine manner.Nature communications · 2023Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Although acute lung injury (ALI) contributes significantly to critical illness, resolution often occurs spontaneously through endogenous pathways. We recently found that mechanical ventilation increases levels of pulmonary adenosine, a signaling molecule known to attenuate lung inflammation. In this study, we hypothesized a contribution of transcriptionally controlled pathways to pulmonary adenosine receptor (ADOR) signaling during ALI. We gained initial insight from microarray analysis of pulmonary epithelia exposed to conditions of cyclic mechanical stretch, a mimic for ventilation-induced lung disease. Surprisingly, these studies revealed a selective induction of the ADORA2B. Using real-time RT-PCR and Western blotting, we confirmed an up to 9-fold induction of the ADORA2B following cyclic mechanical stretch (A549, Calu-3, or human primary alveolar epithelial cells). Studies using ADORA2B promoter constructs identified a prominent region within the ADORA2B promoter conveying stretch responsiveness. This region of the promoter contained a binding site for the transcription factor hypoxia-inducible factor (HIF)-1. Additional studies using site-directed mutagenesis or transcription factor binding assays demonstrated a functional role for HIF-1 in stretch-induced increases of ADORA2B expression. Moreover, studies of ventilator-induced lung injury revealed induction of the ADORA2B during ALI in vivo that was abolished following HIF inhibition or genetic deletion of Hif1a. Together, these studies implicate HIF in the transcriptional control of pulmonary adenosine signaling during ALI.
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