ArticleJCI insight2023
Role of succinate in airway epithelial cell regulation following traumatic lung injury.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- The plasma metabolome and clinical features of patients with coeliac disease in Northwest China.Annals of medicine · 2026Article
- Epithelial-immune interface in asthma: Mechanistic insights driving novel therapeutic strategies.Seminars in immunopathology · 2026Review
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- Recent understanding of immunometabolic remodeling in pulmonary macrophages: homeostasis, chronic respiratory diseases, and therapeutic targeting.Frontiers in pharmacology · 2026Review
- Review
- Succinate aggravates pulmonary fibrosis through the succinate/SUCNR1 axis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies.MedComm · 2025Review
- Unlocking the secrets of glucose metabolism reprogramming: the role in pulmonary diseases.Frontiers in pharmacology · 2025Review
- Early invasive mechanical ventilation improves 28-day clinical outcomes in patients with severe pneumonia complicated by gastrointestinal dysfunction.American journal of translational research · 2025Article
- Identification of potential biomarkers and pathways involved in high-altitude pulmonary edema using GC-MS and LC-MS metabolomic methods.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Lung contusion and gastric aspiration (LC and GA) are major risk factors for developing acute respiratory distress following trauma. Hypoxia from lung injury is mainly regulated by hypoxia-inducible factor 1α (HIF-1α). Published data from our group indicate that HIF-1α regulation in airway epithelial cells (AEC) drives the acute inflammatory response following LC and GA. Metabolomic profiling and metabolic flux of Type II AEC following LC revealed marked increases in glycolytic and TCA intermediates in vivo and in vitro that were HIF-1α dependent. GLUT-1/4 expression was also increased in HIF-1α+/+ mice, suggesting that increased glucose entry may contribute to increased intermediates. Importantly, lactate incubation in vitro on Type II cells did not significantly increase the inflammatory byproduct IL-1β. Contrastingly, succinate had a direct proinflammatory effect on human small AEC by IL-1β generation in vitro. This effect was reversed by dimethylmalonate, suggesting an important role for succinate dehydrogenase in mediating HIF-1α effects. We confirmed the presence of the only known receptor for succinate binding, SUCNR1, on Type II AEC. These results support the hypothesis that succinate drives HIF-1α-mediated airway inflammation following LC. This is the first report to our knowledge of direct proinflammatory activation of succinate in nonimmune cells such as Type II AEC in direct lung injury models.
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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.