ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
PFKFB2-Driven Glycolysis Promotes Dendritic Cell Maturation and Exacerbates Acute Lung Injury.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Intermittent Hypoxia Exacerbates Lipopolysaccharide-Induced Neurobehavioral Abnormalities: The Role of Neuroinflammation and Synaptic-Related Proteins.Brain and behavior · 2026Article
- Small intracellular vesicle-liposome fusogenic nanoplatform sIVs-LPs@Hes: Nebulized delivery targeting pulmonary inflammatory microenvironment to improve ALI.Materials today. Bio · 2026Article
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- Multifunctional nano-platform for precision treatment of acute lung injury via synergistic anti-inflammation and oxidative stress modulation.Journal of nanobiotechnology · 2026Article
- Review
- Review
- Microvesicle release drives cycles of mitophagy flux disruption and inflammatory amplification in sepsis-induced myocardial dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Novel Soluble Guanylate Cyclase Stimulator Attenuates Acute Lung Injury via Inhibiting Pericyte Phenotypic Transition.International journal of molecular sciences · 2026Article
- Nebulized bone marrow-derived stem cell supernatant induces tolerogenic dendritic cells via upregulation of FOXO3 for EAE treatment.Journal of neuroinflammation · 2026Article
- Mitochondrial dysfunction in ARDS: unraveling the regulatory networks and therapeutic opportunities.Frontiers in immunology · 2026Review
- Dendritic cells in cancer immunotherapy: functional barriers, reprogramming strategies and translational challenges.Frontiers in immunology · 2026Review
- Hypoxia-driven tumor immune escape: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Glycolysis in the tumor microenvironment shapes dendritic cell function and antitumor immunity.Frontiers in immunology · 2026Review
- PFKFB2-Driven Glycolysis Promotes Dendritic Cell Maturation and Exacerbates Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- New Exploration of Therapeutic Targets for Radiation Pneumonitis: Comparative Analysis of Molecular Pathways in Radiation-Induced and LPS-Induced Pneumonitis.International journal of medical sciences · 2025Review
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Authors and funding
18 authors.
Funding
Abstract
Acute lung injury (ALI) is a life-threatening condition with excessive immune activation and dysregulated inflammation. Dendritic cells (DCs) play a pivotal role in immune regulation; however, their exact contribution to ALI pathogenesis remains unclear. This study demonstrates that the upregulation of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2) by hypoxia-inducible factor-1α (HIF-1α) enhances glycolysis, drives DC maturation, and exacerbates inflammation, contributing to the pathogenesis of ALI. The findings reveal that HIF-1α directly binds to the PFKFB2 promoter and drives its transcription, leading to increased glycolysis, accelerated DC maturation, and amplified immune activation. In paraquat (PQ)-ALI and lipopolysaccharide (LPS)-ALI mouse models, DC-specific PFKFB2 knockout and DC-targeted delivery of HIF-1α inhibitor-loaded nanoparticles each significantly suppressed DC maturation and alleviated ALI severity. Analyses of lung tissues from patients with PQ poisoning, secondary bacterial pneumonia (2°BP), and Coronavirus Disease 2019 (COVID-19), as well as from normal controls, confirmed these findings, showing increased PFKFB2 expression and DC maturation during ALI. These findings highlight the HIF-1α-PFKFB2 signaling pathway as a critical regulator of glycolysis-driven DC maturation and immune activation, offering novel insights into immunometabolic regulation and a promising therapeutic target for 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 Socratic graph.