A new study published in Burns & Trauma reveals a molecular pathway that drives the formation of fibrotic scars after spinal cord injury (SCI), offering potential targets for therapy. Fibrotic scarring is a major barrier to spinal cord repair; while early scar formation helps stabilize the wound, excessive fibrosis later blocks axon regrowth and limits functional recovery. The research team, from institutions including the Second Affiliated Hospital of Naval Medical University and Shanghai Jiao Tong University School of Medicine, identified the c-Jun–Irf8–CD36 signaling cascade as a key driver of this pathological scarring.
Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, the researchers mapped CD36 expression after SCI and found it concentrated in lesion scars, particularly in fibroblast subpopulations associated with fibrotic progression. To test therapeutic potential, they used salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an AP-1/c-Jun inhibitor, in mouse SCI models. SAB reduced fibroblast accumulation, decreased fibrotic deposition, enhanced angiogenesis, supported axonal regrowth, and improved hindlimb functional recovery. T5224 similarly lowered CD36 expression, reduced fibrosis, promoted vascular remodeling, and improved early motor recovery.
Mechanistically, the study showed that c-Jun activates Irf8, which then promotes CD36 transcription, establishing the c-Jun–Irf8–CD36 axis. CUT&Tag and dual-luciferase reporter assays confirmed this regulatory connection. Multi-omic analyses further indicated 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 removing scar tissue entirely, the goal may be to tune the scar at the right stage—preserving its early protective role while preventing long-term fibrotic barrier formation. Identifying c-Jun, Irf8, and CD36 as connected control points provides a clearer route for developing therapies that reshape the injury microenvironment. Both CD36 and c-Jun are pharmacologically targetable, laying a foundation for localized drug delivery or combination therapies. Further validation in larger animal models is needed before translation to human therapy.
The study is published in Burns & Trauma (DOI: 10.1093/burnst/tkag020). Funding was provided by the National Major Project of Research and Development, China Postdoctoral Science Foundation, and other sources. For more information, visit Chuanlink Innovations.
