LKB1影响CRMP1磷酸化修饰在周围神经损伤后修复过程中的意义

Schwann细胞迁移、分化是周围神经损伤后再生修复的关键。代谢调节基因LKB1能促进Schwann细胞对轴突的髓鞘化，而有关其本身的上下游事件还未被阐明。课题组的前期研究发现参与周围神经再生的塌陷反应调节蛋白CRMP1能与LKB1相互作用。拟提出LKB1出核调节CRMP1磷酸化修饰，影响Schwann细胞迁移、分化，从而参与周围神经损伤后修复的假说。本课题拟首先检测周围神经损伤修复过程中二者的表达，分析它们与周围神经再生的相关性；接着分析二者的相互作用情况和调节关系，并干预该调节通路分析其对Schwann细胞迁移、分化的影响。最后整体干预该信号通路，检测其对周围神经再生修复的影响。本研究将与课题组的前期研究相结合，进一步阐明周围神经再生的分子机制，为周围神经损伤的康复提供新的思路。

Schwann cell migration, differentiation are crucial to the repair and regeneration of peripheral nerve after injury. Metabolic regulator LKB1 can promote Schwann cell–mediated axon maintenance, while its upstream and downstream event are unclear. Our previous studies found that Collapsin Response Mediator Protein 1 which participated in peripheral nerve regeneration could combine with LKB1. Therefore our group put forward the hypothesis that LKB1 regulates CRMP1 phosphorylation, thus influences Schwann cell migration, differentiation, which is helpful to the peripheral nerve regeneration after injury. First, Our studies will detect LKB1 and CRMP1 expression in the process of regeneration after peripheral nerve injury, as well as their relations, interaction and regulation. Then, we analyze their effect on migration, differentiation of Schwann cells by interventing this pathway. Finally our studies detect their effect on the regeneration of peripheral nerve regeneration through the overall intervention in this signaling pathway. The completion of the subject will further understand the molecular mechanisms of peripheral nerve regeneration and provide new ideas for the rehabilitation of peripheral nerve injury.