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), offering potential therapeutic targets to improve 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, shows that the c-Jun–Irf8–CD36 signaling cascade is central to the formation of dense scar tissue that blocks nerve regeneration.
Spinal cord injury often leads to permanent motor and sensory deficits because the damaged tissue does not heal like peripheral tissues. While early scar formation can stabilize the wound and limit inflammation, excessive fibrosis later creates a physical and biochemical barrier that prevents axon regrowth. Current treatments, such as decompression surgery and anti-inflammatory drugs, aim to reduce secondary damage but do not directly address scar remodeling.
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. They tested two inhibitors in mouse models: salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an AP-1/c-Jun inhibitor. Both treatments reduced fibroblast accumulation, decreased fibrotic deposition, enhanced angiogenesis, supported axonal regrowth, and improved hindlimb functional recovery. Mechanistically, the study showed that c-Jun activates Irf8, which then promotes CD36 transcription, establishing the c-Jun–Irf8–CD36 cascade. CUT&Tag and dual-luciferase reporter assays confirmed this regulatory connection.
The findings suggest a more precise approach to managing spinal cord scars. Rather than removing scar tissue entirely, the goal may be to modulate it at the right stage—preserving its early protective role while preventing fibroblasts from building a long-lasting fibrotic wall. Because both CD36 and c-Jun are pharmacologically targetable, this work provides a foundation for developing stage-adapted therapies, including localized drug delivery or combination treatments that target pathogenic fibroblast subtypes while maintaining tissue stability.
“Identifying 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 authors said. The study also highlights how scRNA-seq and spatial transcriptomics can 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 therapy.
The research was supported by several Chinese funding agencies, including the National Major Project of Research and Development and the National Natural Science Foundation of China. The full study is available online at https://doi.org/10.1093/burnst/tkag020.
