Inhibition of CD44 suppresses the formation of fibrotic scar after spinal cord injury via the JAK2/STAT3 signaling pathway
Jin Guo,
Tuo Yang,
Weizhong Zhang,
Kaiming Yu,
Xiong Xu,
Weizhen Li,
Lili Song,
Xiaosong Gu,
Rangjuan Cao,
Shusen Cui
Affiliations
Jin Guo
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China
Tuo Yang
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China
Weizhong Zhang
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China
Kaiming Yu
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China
Xiong Xu
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China
Weizhen Li
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China
Lili Song
Department of Hand & Microsurgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
Xiaosong Gu
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China; Corresponding author
Rangjuan Cao
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China; Corresponding author
Shusen Cui
Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China; Key Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, Jilin Province 130033, China; Corresponding author
Summary: Fibrotic scar is one of the main impediments to axon regeneration following spinal cord injury (SCI). In this study, we found that CD44 was upregulated during the formation of fibrotic scar, and blocking CD44 by IM7 caused downregulation of fibrosis-related extracellular matrix proteins at both 2 and 12 weeks post-spinal cord injury. More Biotinylated dextran amine (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 Basso Mouse Scale (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 SCI.
