Inhibition of CD44 suppresses the formation of fibrotic scar after spinal cord injury via the JAK2/STAT3 signaling pathway

Fibrotic scar is one of the main impediments to axon regeneration following spinal cord injury. In this study, we found that CD44 was up-regulated during the formation of fibrotic scar, and blocking CD44 by IM7 caused down-regulation of fibrosis-related extracellular matrix proteins at both 2 and 12 weeks post-spinal cord injury. More BDA-traced corticospinal tract axons crossed the scar area and extended into the distal region after IM7 administration. A recovery of motor and sensory function was observed based on BMS scores and tail-flick test. In vitro experiments revealed that inhibiting CD44 and JAK2/STAT3 signaling pathway decreased the proliferation, differentiation, and migration of fibroblasts induced by the inflammatory supernatant. Collectively, these findings highlight the critical role of CD44 and its downstream JAK2/STAT3 signaling pathway in fibrotic scar formation, suggesting a potential therapeutic target for spinal cord injury.