A new study published in Burns & Trauma identifies the c-Jun–Irf8–CD36 signaling axis as a key driver of fibrotic scarring after spinal cord injury (SCI), offering a potential therapeutic target to improve repair. Fibrotic scarring is a major barrier to axon regrowth and functional recovery after SCI. While early scar formation helps stabilize the wound, excessive fibrosis later creates a dense barrier that blocks regeneration. The study, led by researchers from multiple Chinese institutions, used single-cell RNA sequencing and spatial transcriptomics to map CD36 expression in mouse SCI models, finding it concentrated in fibroblast subpopulations within lesion scars.
The researchers tested two inhibitors: salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an AP-1/c-Jun inhibitor. Both treatments reduced fibrotic scar formation, improved vascular remodeling, supported axonal regeneration, and enhanced hindlimb motor recovery. Mechanistically, the study showed that c-Jun activates Irf8, which then promotes CD36 transcription, establishing a c-Jun–Irf8–CD36 cascade. CUT&Tag and dual-luciferase assays confirmed this regulatory connection.
According to the authors, the findings suggest a more precise approach to spinal cord scars: rather than removing scar tissue entirely, the goal may be to modulate the scar at the right stage, preserving its early protective role while preventing persistent fibrosis. Because both CD36 and c-Jun are pharmacologically targetable, the work provides a foundation for developing stage-adapted therapies. The study also highlights how single-cell and spatial transcriptomics can reveal cell-specific changes after treatment.
The research was supported by several grants, including the National Major Project of Research and Development (2022YFA1105500) and the National Natural Science Foundation of China. The full study can be accessed at https://doi.org/10.1093/burnst/tkag020.
Further validation in larger animal models and preclinical systems will be needed before translation to human SCI therapy, but the identification of this molecular pathway opens new avenues for drug development aimed at reshaping the injury microenvironment.
