转录因子c-Jun介导CXCL12基因调控雪旺氏细胞修复面神经缺损的自噬机制研究

面神经损伤触发雪旺氏细胞自噬、转化、重塑并最终形成髓鞘是面神经功能修复的基础，但由于雪旺氏细胞取材及培养困难，不易于临床应用，所以本课题将研究的重点聚焦于雪旺氏细胞的自噬和迁移能力上。课题组前期研究发现CXCL12作为内源性神经趋化因子，能促进雪旺氏细胞自身CXCL12基因的高表达，从而使得外源CXCL12因子在与雪旺氏细胞的作用过程中形成正反馈，加速雪旺氏细胞的自噬和迁移，但CXCL12的调控机制并不清楚。基于JARSPAR网站对CXCL12基因转录因子的预测，预实验已证实面神经损伤后转录因子c-Jun与CXCL12蛋白表达均明显上调，故我们推测转录因子c-Jun可以通过介导CXCL12的正反馈调控，加速面神经再生修复。本项目采用特异性微小RNA和慢病毒介导的基因转染技术双向调控c-Jun表达，观察再生神经自噬、面肌电活动等生物学行为，为面神经移植修复的自噬信号通路临床转化奠定理论基础。

The autophagy, transformation, remodeling and myelination of Schwann cells triggered by facial nerve injury are considered as the basis of facial nerve functional repair. However, it is difficult for Schwann cells to obtain materials and culture, so it is not easy for clinical application. Therefore, this research focuses on autophagy and the migration ability of Schwann cells. The previous study of the research group found that CXCL12, as an endogenous chemotactic factor, can promote the high expression of CXCL12 gene in Schwann cells, which makes the exogenous CXCL12 factor form a positive feedback loop in the process of interaction with Schwann cells to accelerate the migration and autophagy of Schwann cells. However, the regulatory mechanism of CXCL12 is not clear. Based on the prediction of transcription factors regulating CXCL12 gene by JARSPAR website, the pilot experiment showed that the expression of transcription factor c-jun and CXCL12 protein were increased after facial nerve injury. Therefore, we speculated that transcription factor c-Jun could promote autophagy and migration of Schwann cells by mediating positive feedback regulation of CXCL12 to accelerate the repair of damaged facial nerve. To evaluate this hypothesis, this project intends to apply specific microRNA and lentiviral-mediated gene transfection technology to bi-directionally regulate c-Jun protein expression, and then observe biological behaviors such as the changes of autophagy in facial neurons and regenerated nerves, and facial myoelectric activity, to explore the signal pathway of functional repair of facial nerve，thus providing the theoretical and applied basis for the clinical functional repair of facial nerve grafting and new ideas for the repair of other peripheral nerve grafting.