Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis-Induced Acute Lung Injury.

ABSTRACT: Circulating lactate is a critical biomarker for sepsis-induced acute lung injury (S-ALI) and is strongly associated with poor prognosis. However, whether elevated lactate directly promotes S-ALI and the specific mechanism involved remain unclear. Here, this work shows that lactate causes pulmonary endothelial glycocalyx degradation and worsens ALI during sepsis. Mechanistically, lactate increases the lactylation of K18 of histone H3, which is enriched at the promoter of EGR1 and promotes its transcription, leading to upregulation of heparanase in pulmonary microvascular endothelial cells. In addition, multiple lactylation sites are identified in EGR1, and lactylation is confirmed to occur mainly at K364. K364 lactylation of EGR1 facilitates its interaction with importin-α, in turn promotin

SUBMITTER: Lu Z 

PROVIDER: S-EPMC11831459 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature