Macrophage polarization-related gene SOAT1 is involved in inflammatory response and functional recovery after spinal cord injury.

Abstract

Macrophages polarization play crucial roles in regulating inflammation and functional recovery after spinal cord injury (SCI). This study aimed to investigate the key macrophage polarization-related genes (MPRGs) for the treatment of SCI. Our research involved identifying differentially expressed genes (DEGs), using immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and machine learning to screening out key MPRGs in the GSE5296. The discriminative potential of MPRGs were validated using expression analysis and receiver operating characteristic (ROC) curves in the GSE45376, while the distribution of hub MPRGs in different cell subtypes were visualized in the single-cell dataset GSE189070. The relationship between the MPRGs and immune infiltration was investigated through correlation analysis. Finally, we detected the effect of blocking sterol O-acyltransferase 1 (SOAT1) on macrophage polarization and functional recovery of SCI. A total of 52 MPRGs were identified. Elevated immune infiltration levels and activation of macrophage-associated biological pathways were noted after SCI. Machine learning determined SOAT1, LGALS3, HAVCR2, IRF8 and PTPRC as the hub MPRGs. External validation confirmed their expression, robust predictive value and distribution patterns. Immune infiltration analysis highlighted the strong correlation between SOAT1 and macrophages. Further, inhibiting of SOAT1 could enhance M2 macrophage polarization, improve inflammatory environment and promote functional recovery of SCI. Our study enhances the understanding of macrophage polarization-related genes in the inflammatory responses of SCI. Targeting SOAT1 emerges as a promising therapeutic strategy for SCI repair.