Identification of Regeneration and Hub Genes and Pathways at Different Time Points after Spinal Cord Injury

Mol Neurobiol. 2021 Jun;58(6):2643-2662. doi: 10.1007/s12035-021-02289-x. Epub 2021 Jan 23.

Abstract

Spinal cord injury (SCI) is a neurological injury that can cause neuronal loss around the lesion site and leads to locomotive and sensory deficits. However, the underlying molecular mechanisms remain unclear. This study aimed to verify differential gene time-course expression in SCI and provide new insights for gene-level studies. We downloaded two rat expression profiles (GSE464 and GSE45006) from the Gene Expression Omnibus database, including 1 day, 3 days, 7 days, and 14 days post-SCI, along with thoracic spinal cord data for analysis. At each time point, gene integration was performed using "batch normalization." The raw data were standardized, and differentially expressed genes at the different time points versus the control were analyzed by Gene Ontology enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene set enrichment analysis. A protein-protein interaction network was then built and visualized. In addition, ten hub genes were identified at each time point. Among them, Gnb5, Gng8, Agt, Gnai1, and Psap lack correlation studies in SCI and deserve further investigation. Finally, we screened and analyzed genes for tissue repair, reconstruction, and regeneration and found that Anxa1, Snap25, and Spp1 were closely related to repair and regeneration after SCI. In conclusion, hub genes, signaling pathways, and regeneration genes involved in secondary SCI were identified in our study. These results may be useful for understanding SCI-related biological processes and the development of targeted intervention strategies.

Keywords: Gene Ontology’s (GO’s) enrichment analysis; Gene set enrichment analysis (GSEA); Hub gene; Kyoto Encyclopedia of Genes and Genomes pathway (KEGG); Regeneration; Spinal cord injury (SCI).

MeSH terms

  • Animals
  • Databases, Genetic
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Gene Ontology
  • Gene Regulatory Networks*
  • Male
  • Nerve Regeneration / genetics*
  • Protein Interaction Maps / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / genetics*
  • Time Factors
  • Up-Regulation / genetics