A new study published in Burns & Trauma on March 12, 2026, identifies a key molecular pathway that drives fibrotic scarring after spinal cord injury (SCI) and demonstrates that targeting this pathway can improve tissue repair and motor recovery. The research, conducted by a team from multiple Chinese institutions including the Second Affiliated Hospital of Naval Medical University and Shanghai Jiao Tong University School of Medicine, offers a new approach to treating SCI by modulating scar formation rather than eliminating it entirely.
Fibrotic scarring is a major barrier to spinal cord repair. While initial scar formation helps stabilize the wound, excessive fibrosis later creates a dense barrier that blocks axon regrowth and limits functional recovery. The study reveals that the c-Jun–Irf8–CD36 axis is central to 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 specific fibroblast subclusters associated with fibrotic progression.
To test therapeutic potential, the team used salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an activator protein-1 (AP-1)/c-Jun inhibitor, in mouse SCI models. Both treatments reduced fibrotic deposition and promoted repair. SAB decreased P4HB-positive fibroblast accumulation, enhanced CD31-marked angiogenesis, supported axonal regrowth, and improved hindlimb functional recovery. T5224 lowered CD36 expression, reduced fibroblast aggregation and ECM deposition, promoted vascular remodeling, and improved early motor recovery. Mechanistically, the study confirmed that c-Jun activates Irf8, which then promotes CD36 transcription, establishing a c-Jun–Irf8–CD36 signaling cascade.
The authors emphasize that the goal is not to remove scars entirely but to tune them at the right stage—preserving their early protective role while preventing long-term fibrotic barriers. This stage-adapted strategy could reshape the injury microenvironment and give regenerating axons a better chance to reconnect. The findings suggest that both CD36 and c-Jun are pharmacologically targetable, providing a foundation for developing localized drug delivery, combination therapy, or precision approaches that act on pathogenic fibroblast subtypes while preserving tissue stability.
This study also highlights the power of advanced genomic techniques like scRNA-seq and spatial transcriptomics to reveal not only which cells are present 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 research was supported by multiple grants, including the National Major Project of Research and Development and the National Natural Science Foundation of China.
The study can be accessed at https://doi.org/10.1093/burnst/tkag020.
