Melatonin promotes Schwann cell proliferation and migration via the shh signalling pathway after peripheral nerve injury
Melatonin promotes Schwann cell proliferation and migration via the shh signalling pathway after peripheral nerve injury
复制标题
褪黑素通过 shh 信号通路促进周围神经损伤后雪旺细胞增殖和迁移
DOI：
10.1111/ejn.14998
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发表时间：
2020-10-22
影响因子：
3.4
通讯作者：
Guo, Kaijin
中科院分区：
文献类型：
--
作者：
Pan, Bin;Jing, Li;Guo, Kaijin
周围神经损伤是临床上常见的疑难杂症，但现有的治疗方法效果并不理想。因此，有必要探索新的治疗方法。为探讨褪黑素在周围神经再生中的作用及其机制，我们采用腹腔注射褪黑素的方法对PNI小鼠进行治疗。我们应用基因芯片技术检测褪黑素对坐骨神经损伤小鼠基因表达的影响。然后，通过基因本体论和蛋白质相互作用的方法筛选出与周围神经再生相关的关键基因。在体外雪旺细胞中进行细胞生物学和分子生物学实验，以验证微阵列分析所识别的关键基因。结果表明，在小鼠坐骨神经损伤后，皮下注射褪黑素后，共检测到598个差异表达基因。生物信息学分析表明Shh基因可能是褪黑素促进周围神经再生的关键基因。体外实验中，褪黑素组雪旺细胞的增殖和迁移能力明显高于对照组，而褪黑素和Luzindole（一种Shh信号通路抑制剂）共同作用后，雪旺细胞的增殖和迁移能力均低于褪黑素组。我们的研究表明，褪黑激素可能通过Shh信号通路促进PNI后雪旺细胞的增殖和迁移，从而促进周围神经再生。本研究为PNI的临床治疗提供了新的途径和靶点。
Peripheral nerve injury (PNI) is a common and incurable disease in the clinic, but the effects of available treatments are still not satisfactory. Therefore, it is necessary to explore new treatment methods. To explore the effect and mechanism of melatonin in peripheral nerve regeneration, we administered melatonin to mice with PNI by intraperitoneal injection. We applied microarray analysis to detect differentially expressed genes of mice with sciatic nerve injury after melatonin application. Then, we conducted gene ontology and protein-protein interactions to screen out the key genes related to peripheral nerve regeneration. Cell biology and molecular biology experiments were performed in Schwann cells in vitro to verify the key genes identified by microarray analysis. Our results showed that a total of 598 differentially expressed genes were detected after melatonin subcutaneously injecting into mice with sciatic nerve injury. Bioinformatics analysis showed that Shh may be the key gene for the promotion of peripheral nerve regeneration by melatonin. In vitro, the proliferation and migration abilities of schwann cells in the melatonin group were significantly higher than those of Schwann cells in the control group; while after treating with both melatonin and luzindole (a Shh signalling pathway inhibitor), the proliferation and migration abilities of Schwann cells decreased compared with the melatonin group. Our study suggests that melatonin might improve the proliferation and migration of Schwann cells via the Shh signalling pathway after PNI, thus promoting peripheral nerve regeneration. Our study provides a new approach and target for the clinical treatment of PNI.