biostudies-literatureYuan Dthe Funding for Scientific Research and Innovation Team of the First Affiliated Hospital of Zhengzhou UniversityNational Natural Science Foundation of Chinae02428https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499423biostudies-literatureUnknown12(37)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 Advanced science (Weinheim, Baden-Wurttemberg, Germany)PFKFB2-Driven Glycolysis Promotes Dendritic Cell Maturation and Exacerbates Acute Lung Injury.PMC1249942382172180;82302483;82472239;82402576;82372215QNCXTD2023004Du YZhu HZhang MPang XYang FCheng YJiang PYuan DHou LJiang YGuo MLi YGuo JZhang YGao YHao HYan HWu YfalsePFKFB2-Driven Glycolysis Promotes Dendritic Cell Maturation and Exacerbates Acute Lung Injury.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 2025-01-01T00:00:00Z2025 Oct2026-07-15T05:51:55.605Z2026-06-30T03:16:14.779ZS-EPMC124994234073606310.1002/advs.202502428