A new study published in Burns & Trauma identifies a molecular pathway that drives fibrotic scarring after spinal cord injury (SCI) and shows that targeting this pathway can reduce scarring and promote functional recovery in mice. The research, led by a team from multiple Chinese institutions, reveals the c-Jun–Irf8–CD36 signaling cascade as a key driver of the excessive fibrosis that forms a barrier to nerve regeneration.
Fibrotic scarring is a major obstacle to spinal cord repair. While initial scar formation helps stabilize the injury, persistent fibroblast activation leads to dense extracellular matrix deposition that blocks axon regrowth. The researchers used single-cell RNA sequencing and spatial transcriptomics to map CD36 expression after SCI, finding it concentrated in specific fibroblast subpopulations within lesion scars.
To test therapeutic potential, the team used two inhibitors in mouse models: salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an AP-1/c-Jun inhibitor. Both treatments reduced fibroblast accumulation, decreased fibrotic deposition, improved blood vessel remodeling, supported axonal regrowth, and enhanced hindlimb motor recovery. Mechanistically, the study showed that c-Jun activates the transcription factor Irf8, which then promotes CD36 expression, establishing the c-Jun–Irf8–CD36 cascade.
“Rather than trying to remove scar tissue completely, the goal may be to tune the scar at the right stage—preserving its early protective role while preventing fibroblasts from building a long-lasting fibrotic wall,” the authors said. They noted that identifying these connected control points provides a clearer route for developing therapies that reshape the injury microenvironment.
These findings suggest new stage-adapted strategies for SCI treatment, particularly therapies targeting scar biology early after injury. Because CD36 and c-Jun are pharmacologically targetable, the work lays a foundation for localized drug delivery or combination therapies that act on pathogenic fibroblasts while preserving tissue stability. The study also demonstrates how advanced genomic techniques can reveal cellular dynamics and treatment effects at high resolution.
Further validation in larger animal models will be needed before clinical translation. The study was supported by multiple Chinese funding agencies and is published in the open-access journal Burns & Trauma. Read the full study for more details.
