A study published in Burns & Trauma on March 12, 2026, reveals that the c-Jun–Irf8–CD36 signaling axis plays a critical role in promoting fibrotic scarring after spinal cord injury (SCI). By combining single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, drug intervention, tissue imaging, and behavioral testing, researchers from multiple institutions in China demonstrated that targeting CD36 or its upstream regulator c-Jun can reduce scar formation, enhance vascular remodeling, support axonal regeneration, and improve motor function in mouse models.
Fibrotic scarring is a major obstacle to spinal cord repair. While initial scar formation helps stabilize the injury site, excessive fibrosis later forms a dense barrier that blocks axon regrowth and limits functional recovery. The study found that CD36, a protein involved in lipid metabolism and inflammatory signaling, is highly expressed in specific fibroblast subpopulations within the lesion scar. Using the CD36 inhibitor salvianolic acid B (SAB) and the AP-1/c-Jun inhibitor T5224, the researchers observed reduced accumulation of P4HB-positive fibroblasts, decreased fibrotic deposition, enhanced CD31-marked angiogenesis, and improved hindlimb functional recovery in treated mice.
Mechanistically, the study established that c-Jun activates the transcription factor Irf8, which in turn promotes CD36 transcription, creating a c-Jun–Irf8–CD36 signaling cascade. CUT&Tag and dual-luciferase reporter assays confirmed this regulatory connection. Multi-omic analyses further showed that T5224 selectively restrained the abnormal expansion of CD36-positive fibroblast subclusters and shifted their transcriptional state toward a less fibrotic, more repair-permissive phenotype.
“These findings suggest a more precise way to think about spinal cord scars,” the authors said. “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.
The study, titled “CD36-enriched fibroblast subpopulations accumulate in lesion scars and can be therapeutically modulated to improve the repair environment,” 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 article is available at https://doi.org/10.1093/burnst/tkag020.
Because both CD36 and c-Jun are pharmacologically targetable, this 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.
