Transection injury differentially alters the proteome of the human sural nerve

Regeneration after severe peripheral nerve injury is often poor. Knowledge of human nerve regeneration and the growth microenvironment is greatly lacking. We aimed to identify the regenerative proteins in human peripheral nerve by comparing the proteome before and after a transection injury. In a unique study design, we collected from the same participants, samples from naïve and degenerating sural nerve. Naïve and degenerating (two weeks after injury) samples were analyzed using mass spectrometry and immunoassays. Using a correlation matrix, we found significantly altered levels following the nerve injury. Mass spectrometry revealed that post-injury samples had 672 proteins significantly upregulated and 661 significantly downregulated compared to naïve samples (q 2). We used Gene Ontology pathways to highlight groups of proteins that were significantly upregulated or downregulated with injury-induced degeneration and regeneration. Significant protein changes in key pathways were identified including growth factor levels, Schwann cell de-differentiation, myelination downregulation, epithelial-mesenchymal transition, and axonal regeneration pathways. Having proteome signatures of human peripheral nerves of both the uninjured and the degenerating/regenerating state may serve as biomarkers to aid in the future development of repair strategies and in monitoring neural tissue regeneration.