2. Academic Validation
  3. Sorafenib promotes sensory conduction function recovery via miR-142-3p/AC9/cAMP axis post dorsal column injury

Sorafenib promotes sensory conduction function recovery via miR-142-3p/AC9/cAMP axis post dorsal column injury

  • Neuropharmacology. 2019 Apr;148:347-357. doi: 10.1016/j.neuropharm.2019.01.031.
Tianyi Wang 1,  Bo Li 2,  Zhijie Wang 3,  Xin Wang 4,  Ziwei Xia 5,  Guangzhi Ning 2,  Xu Wang 2,  Yanjun Zhang 6,  Libin Cui 6,  Mei Yu 7,  Liang Zhang 5,  Zheng Zhang 1,  Wenqi Yuan 8,  Xiaoling Guo 9,  Xin Yuan 10,  Shiqing Feng 11,  Xueming Chen 12
Affiliations

Affiliations

  • 1 Department of Orthopedics, The 981st Hospital of the Chinese People's Liberation Army, Chengde, 067000, Hebei Province, PR China.
  • 2 Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, PR China.
  • 3 Department of Pediatric Internal Medicine, Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei Province, PR China.
  • 4 Chengde Medical University, Chengde, 067000, Hebei Province, PR China.
  • 5 Department of Orthopedics, The Second Hospital of Tianjin Medical University, Tianjin, 300211, PR China.
  • 6 Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China.
  • 7 Leukemia Center, Chinese Academy of Medical Sciences & Peking Union of Medical College, Institute of Hematology & Hospital of Blood Diseases, Tianjin, 30020, PR China.
  • 8 Department of Spinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750000, Ningxia, PR China.
  • 9 Department of Neurology, The 981st Hospital of the Chinese People's Liberation Army, Chengde, 067000, Hebei Province, PR China. Electronic address: 870808116@qq.com.
  • 10 Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China. Electronic address: wtyjjandt@sina.cn.
  • 11 Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, PR China; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, 154 Anshan Road, Heping District, Tianjin, 300052, PR China. Electronic address: professorfengsq@163.com.
  • 12 Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China. Electronic address: sjxfcd@sina.com.
PMID: 30710569 DOI: 10.1016/j.neuropharm.2019.01.031
Abstract

Spinal cord injury results in sensation dysfunction. This study explored miR-142-3p, which acts a critical role in sciatic nerve conditioning injury (SNCI) promoting the repair of the dorsal column injury and validated its function on primary sensory neuron(DRG). miR-142-3p expression increased greatly in the spinal cord dorsal column lesion (SDCL) group and increased slightly in the SNCI group. Subsequently, the expression of Adenylate Cyclase 9 (AC9), the target gene of miR-142-3p, declined sharply in the SDCL group and declined limitedly in the SNCI group. The expression trend of cAMP was opposite to that of miR-142-3p. MiR-142-3p inhibitor improved the axon length, upregulated the expression of AC9, cAMP, p-CREB, IL-6, and GAP43, and downregulated the expression of GTP-RhoA. miR-142-3p inhibitor combined with AC9 siRNA showed shorter axon length, the expression of AC9, cAMP, p-CREB, IL-6, and GAP43 was decreased, and the expression of GTP-RhoA was increased. H89 and AG490, inhibitors of cAMP/PKA pathway and IL6/STAT3/GAP43 axis, respectively, declined the enhanced axonal growth by miR-142-3p inhibitor and altered the expression level of the corresponding proteins. Thus, a substitution therapy using Sorafenib that downregulates the miR-142-3p expression for SNCI was investigated. The results showed the effect of Sorafenib was similar to that of miR-142-3p inhibitor and SNCI on both axon growth in vitro and sensory conduction function recovery in vivo. In conclusion, miR-142-3p acts a pivotal role in SNCI promoting the repair of dorsal column injury. Sorafenib mimics the treatment effect of SNCI via downregulation of miR-142-3p, subsequently, promoting sensory conduction function recovery post dorsal column injury.

Keywords

Axon regeneration; Dorsal column injury; IL-6/STAT3/GAP43 axis; cAMP/PKA pathway; microRNA-142-3p.

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