Gene set enrichment analysis and protein-protein interaction network analysis after sciatic nerve injury

Gene set enrichment analysis and protein-protein interaction network analysis after sciatic nerve injury
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坐骨神经损伤后基因集富集分析和蛋白质-蛋白质相互作用网络分析

DOI:
10.21037/atm-20-4958
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发表时间:
2020-08
影响因子:
--
通讯作者:
Xue Chengbin
Xue Chengbin
中科院分区:
医学4区
文献类型:
--
作者:
Yang Xiaoming;Xu Xi;Cai Xiaodong;He Jin;Lu Panjian;Guo Qi;Wang Gang;Zhu Hui;Wang Hongkui;Xue Chengbin

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背景周围神经损伤后能自发再生。越来越多的研究探讨了周围神经再生的机制,并试图寻找潜在的治疗靶点。现有的各种生物信息学分析工具,基因集富集分析(GSEA)和蛋白质-蛋白质相互作用(PPI)网络可以有效地筛选神经再生的关键靶标。方法通过体外基因表达序列验证和智能通路分析,构建大鼠坐骨神经切断后1、4、7和14 d的GSEA和PPI网络,研究其分子过程。结果免疫应答和相关经典通路的激活被归类为关键生物学事件。此外,神经前体细胞表达发育下调的4-like(NEDD 4L)、神经调节蛋白1(NRG 1)、活化T细胞核因子2(NFATC 2)、中线1(MID 1)、GLI家族锌指2(GLI 2)和腹前同源框1(VAX 1),它们共同参与免疫应答和轴突再生,并验证其在神经损伤后的mRNA和蛋白表达。其中,VAX 1在神经损伤后表达持续增加,被认为是一个潜在的治疗靶点。结论GSEA和PPI网络的联合使用为识别神经再生的潜在治疗靶点提供了一种有价值的方法。
Background Peripheral nerves are able to regenerate spontaneously after injury. An increasing number of studies have investigated the mechanism of peripheral nerve regeneration and attempted to find potential therapeutic targets. The various bioinformatics analysis tools available, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) networks can effectively screen the crucial targets of neuroregeneration. Methods GSEA and PPI networks were constructed through ingenuity pathway analysis and sequential gene expression validation ex vitro to investigate the molecular processes at 1, 4, 7, and 14 days following sciatic nerve transection in rats. Results Immune response and the activation of related canonical pathways were classified as crucial biological events. Additionally, neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), neuregulin 1 (NRG1), nuclear factor of activated T cells 2 (NFATC2), midline 1 (MID1), GLI family zinc finger 2 (GLI2), and ventral anterior homeobox 1 (VAX1), which were jointly involved in both immune response and axonal regeneration, were screened and their mRNA and protein expressions following nerve injury were validated. Among them, the expression of VAX1 continuously increased following nerve injury, and it was considered to be a potential therapeutic target. Conclusions The combined use of GSEA and PPI networks serves as a valuable way to identify potential therapeutic targets for neuroregeneration.
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