A new study published in Burns & Trauma reveals a molecular pathway that drives fibrotic scarring after spinal cord injury (SCI) and demonstrates that targeting this pathway can reduce scar formation and improve functional recovery in mouse models. The research, led by a team from multiple Chinese institutions, identifies the c-Jun–Irf8–CD36 signaling axis as a key regulator of fibrosis in the injured spinal cord.
Fibrotic scarring is a major barrier to repair after SCI. While initial scar formation helps stabilize the wound, excessive fibrosis later creates a dense barrier that blocks axon regrowth. The researchers used single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to map gene expression in the injured spinal cord, finding that CD36 is highly expressed in fibroblast subpopulations within the lesion scar. They then tested two inhibitors: salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an inhibitor of the transcription factor c-Jun. Both treatments reduced fibroblast accumulation, decreased extracellular matrix deposition, enhanced angiogenesis, supported axonal regrowth, and improved hindlimb motor function in mice.
Mechanistically, the study showed that c-Jun activates the transcription factor Irf8, which in turn promotes CD36 expression, forming a signaling cascade. CUT&Tag and dual-luciferase reporter assays confirmed the regulatory connection. Multi-omic analyses revealed that T5224 selectively suppressed the expansion of CD36-positive fibroblast subclusters and shifted their transcriptional state toward a less fibrotic, more repair-permissive phenotype.
“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. The identification of c-Jun, Irf8, and CD36 as connected control points provides a clearer route for developing therapies that reshape the injury microenvironment and give regenerating axons a better chance to reconnect.
The findings may 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 that act on pathogenic fibroblast subtypes while preserving tissue stability. The study also demonstrates how scRNA-seq and spatial transcriptomics can reveal not only which cells are present at an injury site, but where they act and how they change after treatment. Further validation in larger animal models and preclinical systems will be needed before translation to human SCI therapy.
The study was published in Burns & Trauma (DOI: 10.1093/burnst/tkag020) and supported by multiple grants, including the National Major Project of Research and Development and the National Natural Science Foundation of China. The research was conducted by teams from the Second Affiliated Hospital of Naval Medical University, Nantong University, the Second Affiliated Hospital of Nantong University, the Second Affiliated Hospital of Soochow University, and Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine.
