A new study published in Burns & Trauma identifies the c-Jun–Irf8–CD36 axis as a key molecular pathway that drives fibrotic scarring after spinal cord injury (SCI). Fibrotic scarring, while initially stabilizing the wound, later forms a dense barrier that blocks axon regrowth and limits functional recovery. By combining single-cell RNA sequencing, spatial transcriptomics, drug intervention, tissue imaging, and behavioral testing, researchers showed that targeting CD36 or its upstream regulator c-Jun can reduce fibrotic scar formation, improve vascular remodeling, support axonal regeneration, and promote motor recovery in mouse models.
Spinal cord injury often causes long-term motor and sensory deficits because the damaged tissue does not heal like peripheral tissues. After injury, a complex lesion microenvironment forms, involving astrocytes, fibroblasts, immune cells, blood vessels, and extracellular matrix components. Persistent fibroblast activation and extracellular matrix deposition create a physical and biochemical barrier to regeneration. Current clinical approaches mainly aim to reduce secondary damage rather than reshape the scar itself.
The research team, from multiple institutions including the Second Affiliated Hospital of Naval Medical University and Shanghai Ninth People's Hospital, published the study (DOI:10.1093/burnst/tkag020) on 12 March 2026. They used single-cell RNA sequencing and spatial transcriptomic profiling to map CD36 expression after SCI, finding CD36 mainly concentrated in lesion scars and preferentially increased in specific fibroblast subclusters associated with fibrotic progression.
To test therapeutic targeting, the researchers used salvianolic acid B (SAB), a CD36 inhibitor, and T5224, an activator protein-1/c-Jun inhibitor, in mouse SCI models. SAB reduced P4HB-positive fibroblast accumulation, decreased fibrotic deposition, enhanced CD31-marked angiogenesis, supported axonal regrowth, and improved hindlimb functional recovery. T5224 also lowered CD36 expression, reduced fibroblast aggregation and extracellular matrix deposition, promoted vascular remodeling, and improved early motor recovery. Mechanistically, the study showed that c-Jun activates Irf8, and Irf8 then promotes CD36 transcription, establishing a c-Jun–Irf8–CD36 signaling cascade. CUT&Tag and dual-luciferase reporter assays supported this regulatory connection.
The authors suggest that 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. 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.
These 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. Further validation in larger animal models and preclinical systems will be needed before translation to human SCI therapy.
