Work

Mechanism of sepsis regulation by ELANE via macrophage polarization

Year: 2025

Type: article

Abstract: To identify the core immune regulatory gene ELANE in sepsis and explore its mechanism in regulating sepsis through macrophage polarization. Peripheral blood RNA sequencing and bioinformatics analysis were performed on 20 sepsis patients and 10 healthy controls. Differential gene expression (DEGs) screening, functional enrichment (GO/KEGG/GSEA), and protein-protein interaction (PPI) network analysis were conducted. Meta-analysis validated ELANE expression trends across GEO datasets, while survival analysis assessed its prognostic relevance. Single-cell sequencing localized ELANE expression, and in vitro experiments using LPS-stimulated macrophages and siRNA-mediated ELANE inhibition evaluated its role in M1/M2 macrophage polarization and inflammatory factor release (flow cytometry, ELISA). 948 DEGs were identified, with ELANE significantly upregulated in sepsis. PPI and MCC algorithms identified ELANE as a top core gene. Meta-analysis confirmed ELANE overexpression in sepsis, and survival analysis linked high ELANE levels to poor 28-day prognosis. Single-cell sequencing localized ELANE predominantly in macrophages. LPS stimulation increased ELANE expression and M1 polarization (CD86+), while ELANE inhibition reduced M1 polarization and suppressed IL-1β/TNF-α levels. ELANE exacerbates sepsis by promoting M1 macrophage polarization and proinflammatory cytokine release, highlighting its potential as a therapeutic target.

Source: Scientific Reports

DOI: 10.1038/s41598-025-18848-4