Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (2): 434-439.doi: 10.4103/1673-5374.375345

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Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway

Chenxi Zhao1, 2, #, Tiangang Zhou1, 2, #, Ming Li1, 2, #, †, Jie Liu1, 2, Xiaoqing Zhao3, Yilin Pang1, 2, Xinjie Liu1, 2, Jiawei Zhang1, 2, Lei Ma1, 2, Wenxiang Li3, Xue Yao1, 2, 3, *, Shiqing Feng1, 2, 3, *   

  1. 1Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; 2International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; 3Orthopedic Research Center of Shandong University, Cheeloo College of Medicine, Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
  • Online:2024-02-15 Published:2023-08-30
  • Contact: Shiqing Feng, MD, PhD, sqfeng@tmu.edu.cn; Xue Yao, PhD, xueyao@tmu.edu.cn.
  • Supported by:
    This study was supported by the Key Project of the National Natural Science Foundation of China, No. 81930070 (to SF); the National Natural Science Foundation of China, No. 81972074 (to XY); and the Key Program of Natural Science Foundation of Tianjin, No. 19JCZDJC34900 (to XY).

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Abstract: Argatroban is a synthetic thrombin inhibitor approved by U.S. Food and Drug Administration for the treatment of thrombosis. However, whether it plays a role in the repair of spinal cord injury is unknown. In this study, we established a rat model of T10 moderate spinal cord injury using an NYU Impactor Moder III and performed intraperitoneal injection of argatroban for 3 consecutive days. Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord. RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway, which is involved in astrogliosis and glial scar formation. Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway. Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord. Taken together, these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway, thereby promoting the recovery of neurological function after spinal cord injury.

Key words: argatroban, astrogliosis, JAK/STAT signaling pathway, protease-activated receptor-1, spinal cord injury, thrombin, vimentin