LKB1 and CRMP1 cooperatively promote the repair of the sciatic nerve injury
LKB1 and CRMP1 cooperatively promote the repair of the sciatic nerve injury
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DOI：
10.1002/dneu.22932
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发表时间：
2023-12-17
影响因子：
3
通讯作者：
Xu，You-jia
中科院分区：
文献类型：
--
作者：
Liu，Yang;Xu，You-jia
在周围神经系统损伤后，许旺细胞（SC）可以通过提供促进生长的微环境来修复轴突。本研究旨在探讨LKB 1和CRMP 1在坐骨神经损伤修复中的作用及其机制。通过苏木精-伊红染色、RT-PCR、免疫组化和Western blotting检测SNI大鼠LKB 1和CRMP 1的表达变化。免疫荧光结果显示，LKB 1和CRMP 1共定位于SNI大鼠坐骨神经组织的再生轴突中。免疫共沉淀表明LKB 1与CRMP 1相互作用。LKB 1干扰抑制CRMP 1的磷酸化水平。LKB 1和CRMP 1的过表达促进SC的侵袭和迁移，神经细胞突起延伸。模型组大鼠坐骨神经髓鞘结构疏松、紊乱。模型组大鼠痛阈和热敏感反应时间均高于对照组。SNI组神经传导速度、动作电位潜伏期、复合肌肉动作电位峰值明显低于对照组，肌肉萎缩严重。过表达LKB 1可显著改善上述情况。然而，CRMP 1的干扰使LKB 1改善SNI的功能被取消。综上所述，LKB 1与CRMP的相互作用促进了SC的迁移、分化和神经元的延伸，从而改善了神经损伤的修复。
After peripheral nervous system injury, Schwann cells (SCs) can repair axons by providing a growth‐promoting microenvironment. The aim of this study is to explore the effects and mechanisms of LKB1 and CRMP1 on the repair of sciatic nerve injury (SNI). The expressions of LKB1 and CRMP1 were changed in rats with SNI from 12 h to 4 weeks by hematoxylin–eosin staining, RT‐PCR assay, immunohistochemical staining, and western blotting. Immunofluorescence results show that LKB1 and CRMP1 are co‐localized in the regenerated axons of the sciatic nerve tissue of SNI rats. Co‐immunoprecipitation indicates that LKB1 interacts with CRMP1. LKB1 interference suppresses the phosphorylation level of CRMP1. Overexpression of LKB1 and CRMP1 promotes the invasion and migration of SCs, and nerve cell protuberance extends. The structure of the myelin sheath in the sciatic nerve of the model group was found to be loose and disordered. Rats in the model group had higher pain thresholds and heat sensitivity response times than those in the control group. Nerve conduction velocity, the latency of action potential, and the peak value of compound muscle action potential in the SNI group were significantly lower than those in the control group, and the muscle atrophy was severe. Overexpression of LKB1 may significantly improve the above conditions. However, the function of LKB1 to improve SNI is abolished by the interference of CRMP1. In summary, the interaction between LKB1 and CRMP promotes the migration and differentiation of SCs and the extension of neurons, thereby improving the repair of nerve injury.