Pan Bin, Huo Tianqun, Hu Youzhong, Cao Menghan, Bu Xiangbo, Li Ziang, Jing Li, Luo Xuanxiang, Gao Xiao, Feng Hu, Yuan Feng, Guo Kaijin
Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China.
Department of Orthopedics, Kuitun Hospital, Yili Prefecture, Xinjiang 833200,China.
Neuroscience. 2020 Jun 15;437:1-10. doi: 10.1016/j.neuroscience.2020.04.017. Epub 2020 Apr 22.
Peripheral nerve injury (PNI) is a common clinical disease that causes the partial loss of segmental exercise and sensory and autonomic nervous function, placing a heavy burden on patients and their families. A previous study confirmed that exendin-4 can effectively improve nerve regeneration and functional recovery after PNI. However, the specific mechanisms by which exendin-4-mediates this repair have not been clarified. To explore the mechanism of exendin-4 in the treatment of PNI, we used microarray analysis to detect gene expression in the distal segment of the sciatic nerve after sciatic injury. Bioinformatics analyses were used to predict the roles of differentially expressed genes (DEGs) in nerve damage repair. Schwann cells (SCs) were cultured, and we verified the molecular mechanism of exendin-4 in SCs and the effect of exendin-4 on peripheral nerve regeneration through in vitro molecular biology and cell biology experiments. In vivo, exendin-4 could significantly promote peripheral nerve regeneration. A total of 180 DEGs between the exendin-4 group and the control group were detected. Bioinformatics analysis indicated that these DEGs were mainly enriched in the Jak-STAT signaling pathway. In vitro, exendin-4 could significantly promote the proliferation and migration of SCs by activating the Jak-STAT pathway, which promoted peripheral nerve regeneration. Our results indicate that exendin-4 promotes SC proliferation, migration and nerve regeneration after PNI by activating the Jak-STAT pathway. Our findings provide a basis and direction for further elucidation of the mechanisms of exendin-4 in the repair of PNI and provide a new way to treat PNI.
周围神经损伤（PNI）是一种常见的临床疾病，可导致节段性运动、感觉和自主神经功能部分丧失，给患者及其家庭带来沉重负担。先前的一项研究证实，艾塞那肽-4可有效促进周围神经损伤后的神经再生和功能恢复。然而，艾塞那肽-4介导这种修复的具体机制尚未阐明。为了探究艾塞那肽-4治疗周围神经损伤的机制，我们采用微阵列分析检测坐骨神经损伤后坐骨神经远端节段的基因表达。利用生物信息学分析预测差异表达基因（DEGs）在神经损伤修复中的作用。培养雪旺细胞（SCs），并通过体外分子生物学和细胞生物学实验验证艾塞那肽-4在雪旺细胞中的分子机制以及艾塞那肽-4对周围神经再生的影响。在体内，艾塞那肽-4可显著促进周围神经再生。在艾塞那肽-4组和对照组之间共检测到180个差异表达基因。生物信息学分析表明，这些差异表达基因主要富集在Jak-STAT信号通路中。在体外，艾塞那肽-4可通过激活Jak-STAT通路显著促进雪旺细胞的增殖和迁移，从而促进周围神经再生。我们的结果表明，艾塞那肽-4通过激活Jak-STAT通路促进周围神经损伤后的雪旺细胞增殖、迁移和神经再生。我们的研究结果为进一步阐明艾塞那肽-4修复周围神经损伤的机制提供了依据和方向，并为治疗周围神经损伤提供了新的途径。
