A new study published in Burns & Trauma on March 12, 2026, has identified a key molecular pathway that drives fibrotic scarring after spinal cord injury (SCI), offering a potential therapeutic target to improve recovery. The research, conducted by a team from multiple institutions in China, demonstrates that the c-Jun–Irf8–CD36 signaling cascade plays a central role in the formation of dense scar tissue that blocks axon regrowth and limits functional recovery.
Fibrotic scarring is a major obstacle to spinal cord repair. While initial scar formation helps stabilize the injury site and limit inflammation, persistent fibroblast activation leads to excessive extracellular matrix deposition, creating a physical and biochemical barrier. Current clinical approaches focus on reducing secondary damage rather than reshaping the scar itself. To address this, the researchers employed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, drug intervention, tissue imaging, and behavioral testing in mouse models.
The study revealed that CD36-enriched fibroblast subpopulations accumulate in lesion scars. Using two inhibitors—salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an AP-1/c-Jun inhibitor—the team found that blocking CD36 or its upstream regulator c-Jun reduced fibrotic scar formation, improved vascular remodeling, supported axonal regeneration, and enhanced motor recovery. Specifically, SAB reduced P4HB-positive fibroblast accumulation, decreased fibrotic deposition, and improved hindlimb function. T5224 similarly lowered CD36 expression, reduced fibroblast aggregation and ECM deposition, and promoted early motor recovery.
Mechanistically, the study established that c-Jun activates Irf8, which then promotes CD36 transcription, forming a c-Jun–Irf8–CD36 signaling cascade. CUT&Tag and dual-luciferase reporter assays confirmed this regulatory connection. Multi-omic analyses showed that T5224 selectively restrained the abnormal 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 completely removing scar tissue, 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 identification of c-Jun, Irf8, and CD36 as connected control points provides a clearer route for developing therapies that reshape the injury microenvironment.
These findings support new stage-adapted strategies for SCI treatment, especially therapies aimed at scar biology during the early post-injury window. Because both CD36 and c-Jun are pharmacologically targetable, the work provides a foundation for testing localized drug delivery, combination therapy, or precision approaches. Further validation in larger animal models is needed before translation to human therapy. The study is published with DOI 10.1093/burnst/tkag020.
