Rats and axolotls share a common molecular signature after spinal cord injury enriched in collagen-1

Spinal cord injury (SCI) in mammals leads to irreversible tissue damage and loss of function. In contrast, axolotls are able to fully regenerate injured tissues including the spinal cord. To explore new pathological and repair mechanisms, we compared rat versus axolotl transcriptomics microarrays and isolated shared genes that were similarly or differentially regulated between the two species 7 days post-SCI. Functionally distinct groups of genes characterised rat and axolotl transcriptional profiles after spinal injury. Unexpectedly, multiple genes involved in extracellular matrix remodelling, and in particular collagen-1 (type I collagen; COL1A) and collagen-associated molecules, were upregulated in both rats and axolotls after SCI. Given the significance of collagen-1 and matrix remodelling in scarring and fibrosis in mammals, we examined collagen-1 further in rat contusion SCI. High-throughput proteomics analysis validated the persistent and robust expression of the collagen-enriched matrix signature at the protein level. Collagen-1 accumulated abundantly both in early and advanced rat contusion lesions. Surprisingly, collagen-1 accumulation was likely not due to tissue fibrosis but was instead associated with pathological vascular remodelling. The transcription factor SP1 which was upregulated after SCI, was database predicted and further validated to regulate, at least in part, the expression of collagen-1 and associated proteins in rat lesions. Our work reveals the unexpected contribution of collagen-1 and vascular remodelling to scarring in rat contusion SCI. Regulation of collagen and vascular remodelling might represent novel therapeutic targets for blocking or reversing tissue scarring after mammalian SCI.