METTL3-mediated N6-methyladenosine exacerbates ferroptosis via m6A-IGF2BP2-dependent mitochondrial metabolic reprogramming in sepsis-induced acute lung injury.

ABSTRACT: Neutrophil extracellular traps (NETs), released by polymorphonuclear neutrophils (PMNs), exert a robust antimicrobial function in infectious diseases such as sepsis. NETs also contribute to the pathogenesis and exacerbation of sepsis. Although the lung is highly vulnerable to infections, few studies have explored the role of NETs in sepsis-induced acute lung injury (SI-ALI). We demonstrate that NETs induce SI-ALI via enhanced ferroptosis in alveolar epithelial cells. Our findings reveal that the excessive release of NETs in patients and mice with SI-ALI is accompanied by upregulation of ferroptosis depending on METTL3-induced m6A modification of hypoxia-inducible factor-1α (HIF-1α) and subsequent mitochondrial metabolic reprogramming. In addition to conducting METTL3 overexpression and kno

SUBMITTER: Zhang H 

PROVIDER: S-EPMC10504453 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature