基于小鼠肺组织蛋白质组学预测哮喘发病机制及潜在治疗靶点

目的 以蛋白质组学分析为基础，联合网络药理学技术，初步预测哮喘发病的生物学机制及其潜在的核心治疗靶点。方法 采用卵清蛋白诱导和激发，建立小鼠哮喘模型；通过Maxquant检索，获得质谱蛋白和基因数据，方差分析和t检验获得差异蛋白，建立差异蛋白聚类分析图谱及靶点集，构建蛋白互作网络图，通过网络可视化分析，预测哮喘发病机制涉及的靶点、信号通路和生物学过程。结果 蛋白质组学检索得到5063个基因，以模型组基因表达/空白组基因表达≥2且P≤0.05、模型组基因表达/空白组基因表达≤1/2且P≤0.05为条件筛选得到的差异基因共904个，聚类分析分为3簇，模型组与空白组比较，上调基因595个，下调基因309个；哮喘发病机制可能涉及调控代谢、FcγR介导的吞噬、白细胞内皮迁移、肿瘤坏死因子信号通路、Toll样受体信号通路、B细胞受体信号通路、磷脂酰肌醇3激酶/蛋白激酶B信号通路、血管平滑肌收缩和细胞黏附等相关通路；筛选得到的作用靶点包括ITGB3、CYBB、SYK、VWF、ITGB2、MYD88、COMP、VEGFA和FCGR2B;且哮喘病变主要影响信号转导、氧化还原过程、免疫应答、炎症反应、细胞...

Prediction of Pathogenesis and Potential Therapeutic Targets for Asthma Based on Proteomics of Mouse Lung Tissue

Objective To predict the mechanism and potential therapeutic targets of asthma based on proteomic analysis and network pharmacology. Methods The mouse model of asthma was established via intraperitoneal injection of 200 μl suspension containing 100 μg ovalbumin(OVA)and 2 mg aluminum hydroxide and intranasal administration with 5% OVA.Maxquant system was used to retrieve the protein and gene data.The analysis of variance and t test were performed to obtain differential proteins,and then clustering map and target set of differential proteins were established.The protein-protein interaction network of differential proteins was constructed.The pathogenesis of asthma was investigated via gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Results A total of 5063 genes were identified,from which 904 differentially expressed genes were selected with the thresholds of fold change(model/control)≥2 and P≤0.05 as well as thresholds of fold change(model/control)≤1/2 and P≤0.05.The 904 genes were classified into 3 clusters.The 904 differentially expressed genes included 595 up-regulated genes and 309 down-regulated genes in the model group compared with the control group.The pathogenesis of asthma was associated with regulatory metabolism,Fc gamma-R mediated phagocytosis,leukocyte transendothelial migration,tumor necrosis factor signaling pathway,Toll-like receptor signaling pathway,B cell receptor signaling pathway,phosphoinositol 3-kinase/protein kinase B signaling pathway,vascular smooth muscle contraction and cell adhesion signaling pathway.ITGB3,CYBB,SYK,VWF,ITGB2,MYD88,COMP,VEGFA,and FCGR2B were identified as the therapeutic targets for asthma.Meanwhile,the biological processes such as signal transduction,redox process,immune response,inflammatory response,cell adhesion,positive regulation of GTPase activity,apoptosis,and extracellular matrix formation were the main participants in asthma. Conclusion This study systematically revealed the pathogenesis,biological processes,and 9 potential therapeutic targets of asthma.