ArticleJCI insight2022
HIF1A-dependent induction of alveolar epithelial PFKFB3 dampens acute lung injury.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- Identification of HIF1A as a therapeutic target during SARS-CoV-2-associated lung injury.JCI insight · 2025Trial
- Epithelial-immune interface in asthma: Mechanistic insights driving novel therapeutic strategies.Seminars in immunopathology · 2026Review
- 6β-Acetoxysandaracopimaradien-1α,9α-diol Attenuates LPS-Induced Acute Lung Injury: Association with Alterations in Src, MAPK, and Akt/GSK-3β Signalling.International journal of molecular sciences · 2026Article
- Evolution in lung IRI cell death research: a 20-year global bibliometric study (2005-2024).Annals of medicine and surgery (2012) · 2026Review
- Cellular mechanometabolism: stimuli and implications.EMBO reports · 2026Review
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- Lactate dehydrogenase-to-albumin ratio as a potential prognostic indicator in glucocorticoid-treated severe pneumonia: a multicenter retrospective study with external validation.Frontiers in immunology · 2026Article
- Mitochondrial dysfunction in ARDS: unraveling the regulatory networks and therapeutic opportunities.Frontiers in immunology · 2026Review
- Lactate and Lactylation in Respiratory Diseases: from Molecular Mechanisms to Targeted Strategies.Lung · 2025Review
- E-Cadherin: A conductor of cellular signaling.Current opinion in cell biology · 2025Review
- Review
- Review
- Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models.Science translational medicine · 2025Article
- PFKFB3 alleviates the advancement ofFrontiers in cellular and infection microbiology · 2025Article
- Decoding the HIF-1-driven metabolic-inflammatory-immune axis in sepsis-associated lung injury: a comprehensive overview.Frontiers in immunology · 2025Review
- AIDET communication combined with alternating prone ventilation for HIF-1α, sTREM-1 and hs-CRP in awake elderly patients with severe pneumonia.Frontiers in medicine · 2025Article
- Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome.The Journal of physiology · 2024Review
- SubnormothermicJournal of thoracic disease · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Electroacupuncture alleviates ventilator-induced lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.BMC anesthesiology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 5 countries.
Funding
Abstract
Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during injurious mechanical ventilation or acid instillation. Studies in genetic models linked Pfkfb3 expression and function to Hif1a. Not only did intratracheal pyruvate instillation reconstitute Pfkfb3loxP/loxP or Hif1aloxP/loxP SPC-ER-Cre+ mice, but pyruvate was also effective in ALI treatment of wild-type mice. Finally, proof-of-principle studies in human lung biopsies demonstrated increased PFKFB3 staining in injured lungs and colocalized PFKFB3 to alveolar epithelia. These studies reveal a specific role for PFKFB3 in counterbalancing alveolar inflammation and lay the groundwork for novel metabolic therapeutic approaches during ALI.
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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.