Gene set enrichment analysis and protein-protein interaction network analysis after sciatic nerve injury.

Background: Peripheral nerves are able to regenerate spontaneously after injury. An increasing number of studies have investigated the mechanism of peripheral nerve regeneration and attempted to find potential therapeutic targets. The various bioinformatics analysis tools available, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) networks can effectively screen the crucial targets of neuroregeneration.

Methods: GSEA and PPI networks were constructed through ingenuity pathway analysis and sequential gene expression validation to investigate the molecular processes at 1, 4, 7, and 14 days following sciatic nerve transection in rats.

Results: Immune response and the activation of related canonical pathways were classified as crucial biological events. Additionally, neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), neuregulin 1 (NRG1), nuclear factor of activated T cells 2 (NFATC2), midline 1 (MID1), GLI family zinc finger 2 (GLI2), and ventral anterior homeobox 1 (VAX1), which were jointly involved in both immune response and axonal regeneration, were screened and their mRNA and protein expressions following nerve injury were validated. Among them, the expression of VAX1 continuously increased following nerve injury, and it was considered to be a potential therapeutic target.

Conclusions: The combined use of GSEA and PPI networks serves as a valuable way to identify potential therapeutic targets for neuroregeneration.