PFKFB2-Driven Glycolysis Promotes Dendritic Cell Maturation and Exacerbates Acute Lung Injury.

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

SUBMITTER: Yuan D 

PROVIDER: S-EPMC12499423 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature