Liu Tao, Wang Guanying, Zhang Xingping, Liu Xin, Liang Zhengting, Ren Xiaojuan, Yan Deqi, Zhang Wenhui
Traditional Chinese Medicine Hospital Affiliated with Xinjiang Medical University, Ürümqi, China.
Postdoctoral Workstation of Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China.
Front Integr Neurosci. 2022 Jul 26;16:936955. doi: 10.3389/fnint.2022.936955. eCollection 2022.
Insomnia is a clinical problem of significant public health importance; however, the underlying pathogenesis of this disorder is not comprehensively understood.
To identify potential treatment targets and unfold one of the gaps that were involved in insomnia pathological mechanisms, we employed a tandem mass tag-based (TMT) quantitative proteomics technology to detect differentially expressed proteins (DEPs) in serum from patients with insomnia and controls. DEPs were further analyzed by bioinformatics platforms. In addition, parallel reaction monitoring (PRM) was used to verify the TMT results.
Patients with insomnia had poorer sleep quality compared with healthy controls. A total of 106 DEPs were identified among patients with insomnia and controls. They were mainly enriched in immune and inflammation-related biological functions and signaling pathways. Using the protein-protein interaction network, we screened the 10 most connected proteins as key DEPs. We predicted that four key DEPs were subject to targeted regulation by natural compounds of herbs. Eight key DEPs were validated using PRM in an additional 15 patients with insomnia and 15 controls, and the results also supported the experimental findings.
We identified aberrantly expressed proteins in insomnia that may be involved in the immune-inflammatory response. The 10 key DEPs screened may be potential targets for insomnia, especially FN1, EGF, HP, and IGF1. The results of this study will broaden our understanding of the pathological mechanisms of insomnia and provide more possibilities for pharmacotherapy.
失眠是一个具有重大公共卫生意义的临床问题；然而，这种疾病的潜在发病机制尚未得到全面了解。
为了确定潜在的治疗靶点并揭示失眠病理机制中涉及的一个空白，我们采用基于串联质谱标签（TMT）的定量蛋白质组学技术来检测失眠患者和对照组血清中差异表达的蛋白质（DEP）。通过生物信息学平台对DEP进行进一步分析。此外，采用平行反应监测（PRM）来验证TMT结果。
与健康对照组相比，失眠患者的睡眠质量较差。在失眠患者和对照组中总共鉴定出106种DEP。它们主要富集于免疫和炎症相关的生物学功能及信号通路。利用蛋白质-蛋白质相互作用网络，我们筛选出10个连接度最高的蛋白质作为关键DEP。我们预测其中4个关键DEP受草药天然化合物的靶向调控。在另外15例失眠患者和15例对照中使用PRM验证了8个关键DEP，结果也支持了实验发现。
我们鉴定出失眠中异常表达的蛋白质，这些蛋白质可能参与免疫炎症反应。筛选出的10个关键DEP可能是失眠的潜在靶点，尤其是纤连蛋白1（FN1）、表皮生长因子（EGF）、结合珠蛋白（HP）和胰岛素样生长因子1（IGF1）。本研究结果将拓宽我们对失眠病理机制的理解，并为药物治疗提供更多可能性。
