ArticleJCI insight2021
The pentose phosphate pathway mediates hyperoxia-induced lung vascular dysgenesis and alveolar simplification in neonates.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Hyperoxia and pulmonary vascular injury in bronchopulmonary dysplasia: pathogenic mechanisms and emerging therapies-a systematic review.Pediatric research · 2026Pooled it
- Contemporary Endothelial Genome Editing Technologies: Towards Precision Genetic Medicine for Vascular Diseases.International journal of molecular sciences · 2026Review
- PKM2 Promotes Glycolysis in Alveolar Macrophages and Induces Inflammation in Bronchopulmonary Dysplasia.Inflammation · 2026Article
- Monophosphoryl lipid A boosts macrophage antimicrobial immunity by metabolically regulating source-specific ROS generation.Frontiers in immunology · 2026Article
- The Destructive Cycle in Bronchopulmonary Dysplasia: The Rationale for Systems Pharmacology Therapeutics.Antioxidants (Basel, Switzerland) · 2025Review
- Endothelial Cpt1a Inhibits Neonatal Hyperoxia-Induced Pulmonary Vascular Remodeling by Repressing Endothelial-Mesenchymal Transition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From metabolic alterations to chronic inflammation: mechanisms and immunoregulation of metabolic reprogramming in COPD.Frontiers in immunology · 2025Review
- Characterization of the airway microbiome in preterm infants with bronchopulmonary dysplasia.Frontiers in cellular and infection microbiology · 2025Article
- Longitudinal transcriptomic analysis of the hyperoxia-exposed preterm rabbit as a model of BPD.Frontiers in pediatrics · 2025Article
- Activated DRP1 promotes mitochondrial fission and induces glycolysis in ATII cells under hyperoxia.Respiratory research · 2024Article
- Research progress of microvascular development in bronchopulmonary dysplasia.Pediatric investigation · 2024Review
- Visualization of the relationship between metabolism and lung diseases from the perspective of bibliometric analysis: research trends and future prospects.Frontiers in medicine · 2024Article
- Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension.The European respiratory journal · 2023Article
- Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during postnatal growth.iScience · 2023Article
- Timing and cell specificity of senescence drives postnatal lung development and injury.Nature communications · 2023Article
- Interstage Single Ventricle Heart Disease Infants Show Dysregulation in Multiple Metabolic Pathways: Targeted Metabolomics Analysis.JACC. Advances · 2023Article
- Upregulating carnitine palmitoyltransferase 1 attenuates hyperoxia-induced endothelial cell dysfunction and persistent lung injury.Respiratory research · 2022Article
- Characterization of metabolites and biomarkers for the probiotic effects of Clostridium cochlearium on high-fat diet-induced obese C57BL/6 mice.European journal of nutrition · 2022Article
- Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis.International journal of molecular sciences · 2022Review
- Pharmacometabolomics Profiling of Preterm Infants Validates Patterns of Metabolism Associated With Response to Dexamethasone Treatment for Bronchopulmonary Dysplasia.Frontiers in pediatrics · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Dysmorphic pulmonary vascular growth and abnormal endothelial cell (EC) proliferation are paradoxically observed in premature infants with bronchopulmonary dysplasia (BPD), despite vascular pruning. The pentose phosphate pathway (PPP), a metabolic pathway parallel to glycolysis, generates NADPH as a reducing equivalent and ribose 5-phosphate for nucleotide synthesis. It is unknown whether hyperoxia, a known mediator of BPD in rodent models, alters glycolysis and the PPP in lung ECs. We hypothesized that hyperoxia increases glycolysis and the PPP, resulting in abnormal EC proliferation and dysmorphic angiogenesis in neonatal mice. To test this hypothesis, lung ECs and newborn mice were exposed to hyperoxia and allowed to recover in air. Hyperoxia increased glycolysis and the PPP. Increased PPP, but not glycolysis, caused hyperoxia-induced abnormal EC proliferation. Blocking the PPP reduced hyperoxia-induced glucose-derived deoxynucleotide synthesis in cultured ECs. In neonatal mice, hyperoxia-induced abnormal EC proliferation, dysmorphic angiogenesis, and alveolar simplification were augmented by nanoparticle-mediated endothelial overexpression of phosphogluconate dehydrogenase, the second enzyme in the PPP. These effects were attenuated by inhibitors of the PPP. Neonatal hyperoxia augments the PPP, causing abnormal lung EC proliferation, dysmorphic vascular development, and alveolar simplification. These observations provide mechanisms and potential metabolic targets to prevent BPD-associated vascular dysgenesis.
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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.