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.
- 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: [email protected].
- 10. Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China. Electronic address: [email protected].
- 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: [email protected].
- 12. Department of Spine Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 100000, PR China. Electronic address: [email protected].
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.