Interplay of axon regeneration genes and immune infiltration in spinal cord injury.

Background: Spinal Cord Injury (SCI) impacts neural function and regeneration. This study aimed to identify key axon regeneration genes in SCI and their correlations with immune infiltration and SCI subtyping.

Methods: Gene expression profiles of 30 sham-operated mice and 29 SCI mice were obtained from GSE5296, GSE47681, and GSE93561 datasets. A PPI network of axon regeneration genes was constructed. Consensus clustering classified SCI subtypes. Differential expression analysis identified genes associated with SCI and its subtypes. Immune infiltration was assessed. WGCNA identified key genes. Potential drugs targeting hub genes were explored. An SCI mouse model was established and subjected to HE staining to assess pathological changes. The dysregulation of five key axon regeneration-related genes was validated in mouse spinal cord tissues using qRT-PCR and Western blotting.

Results: We identified 2,971 genes associated with SCI, including 19 axon regeneration-related genes, and 144 differentially expressed transcription factors, with Jun being highly interconnected. Significant alterations in immune cell abundance correlated with axon regeneration genes. Consensus clustering stratified SCI samples into two subtypes. WGCNA identified 21 hub genes associated with SCI subtypes. Drug-gene interaction analysis identified Itgam and Ptprc as potential therapeutic targets. Validation experiments showed significant upregulation of Fn1, Sdc1, and Cspg4, and downregulation of Col4a1 and Lamb1 in the SCI model group compared to controls.

Conclusions: Our study elucidates the interplay among axon regeneration genes, immune infiltration, and transcriptional regulation in SCI. Validation experiments confirmed the dysregulation of key axon regeneration-related genes in SCI mice, supporting their role in SCI pathology.