The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis

Abstract

Despite the debilitating consequences following traumatic spinal cord injury (SCI), there is a lack of safe and effective therapeutics in the clinic. The species-specific responses to SCI present major challenges and opportunities for the clinical translation of biomolecular and pharmacological interventions. Recent transcriptional analyses in preclinical SCI studies have provided a snapshot of the local SCI-induced molecular responses in different animal models. However, the variation in the pathogenesis of traumatic SCI across species is yet to be explored. This study aims to identify and characterize the common and inconsistent SCI-induced differentially expressed genes across species to identify potential therapeutic targets of translational relevance. A comprehensive search of open-source transcriptome datasets identified four cross-compatible microarray experiments in rats, mice, and salamanders. We observed consistent expressional changes in extracellular matrix components across the species. Conversely, salamanders showed downregulation of intracellular MAPK signaling compared to rodents. Additionally, sequence conservation and interactome analyses highlighted the well-preserved sequences of Fn1 and Jun with extensive protein-protein interaction networks. Lastly, in vivo immunohistochemical staining for fibronectin was used to validate the observed expressional pattern. These transcriptional changes in extracellular and MAPK pathways present potential therapeutic targets for traumatic SCI with promising translational relevance.