A new study published in Burns & Trauma (DOI:10.1093/burnst/tkag020) identifies a molecular pathway that drives fibrotic scarring after spinal cord injury (SCI), offering potential therapeutic targets to improve repair. Fibrotic scarring is a major barrier to axon regrowth and functional recovery, as excessive fibrosis forms a dense barrier that blocks regeneration. The research team, from multiple institutions including the Second Affiliated Hospital of Naval Medical University and Shanghai Jiao Tong University School of Medicine, used single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, drug intervention, and behavioral testing to uncover the c-Jun–Irf8–CD36 signaling cascade.
After SCI, the lesion microenvironment becomes complex with astrocytes, fibroblasts, immune cells, and extracellular matrix components. While scar formation initially limits inflammation, persistent fibroblast activation leads to a fibrotic wall. The researchers found that CD36, a scavenger receptor, is enriched in fibroblast subpopulations within lesion scars. Using the CD36 inhibitor salvianolic acid B (SAB) and the AP-1/c-Jun inhibitor T5224 in mouse models, they demonstrated reduced fibroblast accumulation, decreased fibrotic deposition, enhanced angiogenesis, and improved hindlimb functional recovery. Mechanistically, c-Jun activates Irf8, which promotes CD36 transcription, establishing the c-Jun–Irf8–CD36 axis.
These findings suggest a more precise approach to spinal cord scar management: rather than removing scar tissue entirely, modulating it at the right stage could preserve its early protective role while preventing long-term fibrosis. The study provides a foundation for developing stage-adapted therapies targeting CD36 or c-Jun, potentially using localized drug delivery or combination therapies. Further validation in larger animal models is needed before clinical translation.
