OGD-Induced Lactylation of H3K9 Contributes to M1 polarization and Inflammation of microglia Through  TNF pathway
Hypoxia-induced M1 polarization of microglia and the resultant inflammatory response are pivotal mechanisms in the development of hypoxic-ischemic encephalopathy (HIE). Recent studies have identified lactylation of histones as a novel epigenetic modification, in which lactate groups are added to lysine residues on histones. Lactate, a product of cellular respiration, accumulates in the cytoplasm when cells experience hypoxia due to the conversion of pyruvate by lactate dehydrogenase. Therefore, histone lactylation may be involved in the pathogenesis of HIE. This study aims to investigate the role and mechanism of histone lactylation in hypoxia-induced M1 polarization of microglia and the associated inflammation, with the goal of providing new insights for the research and treatment of HIE. Overall design: In this study, we examined the effects of oxygen-glucose deprivation (OGD) on microglial polarization using both an HIE animal model and a cell model. The levels of histone lactylation at different lysine residues were detected by Western blot. Microglial polarization and inflammatory cytokines induced by OGD were experimentally verified by immunofluorescence, qPCR, and Western blot. Finally, RNA sequencing, ChIP-qPCR and siRNA was performed to elucidate the potential mechanisms by which H3K9 lactylation regulates M1 polarization of microglia.