Proteomic Signatures of Regeneration: Uncovering Extracellular Matrix-Associated Cues in Goldfish Spinal Cord Repair

Spinal cord injury (SCI) in mammals leads to inflammation, glial scarring, and extracellular matrix (ECM) remodeling that hinder regeneration. In contrast, certain teleosts, such as zebrafish and goldfish (Carassius auratus), exhibit remarkable spinal cord regenerative capabilities and substantial functional recovery following injury. To uncover the molecular basis of this regenerative ability, we performed a proteomic analysis of goldfish spinal cord ECM-enriched post-injury and compared it to literature on mammalian models. We identified a distinct regenerative signature in goldfish, marked by the downregulation of vimentin A2, histone H1-like isoform X1, connexin 43, and biglycan-like proteins, factors typically associated with scarring and inflammation in mammals. Notably, nucleosome assembly protein 1-like 4 (NAP1L4), a chromatin remodeling protein, was uniquely upregulated in goldfish, suggesting a more permissive epigenetic environment for repair. These findings provide new insights into the molecular determinants of successful spinal cord regeneration and may inform strategies for developing regenerative therapies in humans. Teaser: Goldfish spinal cords reveal a unique regenerative proteomic signature absent in non-regenerative mammals after injury.