A new study published in Burns & Trauma has uncovered a molecular pathway that drives excessive scarring after spinal cord injury (SCI), offering potential targets for therapies that could improve recovery. The research, led by a team from multiple Chinese institutions, identifies the c-Jun–Irf8–CD36 signaling cascade as a central mechanism in the formation of fibrotic scars that block nerve regeneration.
Spinal cord injury often leads to permanent motor and sensory deficits because the damaged tissue does not heal like peripheral tissues. While initial scar formation helps stabilize the wound, persistent fibroblast activation and deposition of extracellular matrix components create a dense barrier that prevents axon regrowth. Current treatments focus on reducing secondary damage rather than reshaping the scar itself.
Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, the researchers mapped CD36 expression after SCI and found it concentrated in specific fibroblast subpopulations within lesion scars. They then tested two inhibitors in mouse models: salvianolic acid B (SAB), which targets CD36, and T5224, which inhibits the transcription factor c-Jun. Both treatments reduced fibrotic scar formation, improved blood vessel remodeling, supported axon regrowth, and enhanced hindlimb motor function.
Mechanistically, the study showed that c-Jun activates Irf8, which in turn promotes CD36 transcription, establishing the c-Jun–Irf8–CD36 axis. CUT&Tag and dual-luciferase reporter assays confirmed the regulatory connection. Multi-omic analyses revealed that T5224 selectively reduced the expansion of CD36-positive fibroblast subclusters and shifted their transcriptional state toward a less fibrotic, more repair-permissive phenotype.
The authors suggest that rather than eliminating scar tissue entirely, the goal should be to modulate it at the right stage—preserving its early protective role while preventing the formation of a long-lasting fibrotic wall. Because CD36 and c-Jun are pharmacologically targetable, the findings provide a foundation for developing stage-adapted therapies that act on pathogenic fibroblast subtypes.
The study, published on 12 March 2026, can be accessed here. It was supported by several grants, including the National Major Project of Research and Development and the National Natural Science Foundation of China. Further validation in larger animal models is needed before translation to human therapy.
