基于GEO芯片联合网络药理学探讨当归饮子治疗慢性荨麻疹的cross-talk及miRNA-mRNA机制

To Explore the Cross-talk and miRNA-mRNA Mechanism of Danggui Yinzi in the Treatment of Chronic Urticaria Based on GEO Chip Combined with Network Pharmacology

目的采用GEO芯片联合网络药理学的研究方法,初步探讨当归饮子治疗慢性荨麻疹(CU)的cross-talk及miRNA-mRNA机制,为后续实验研究提供理论基础。方法采用R语言limma包对GSE57178芯片进行差异分析;采用TCMSP、TCMID、PubChem、String、DAVID、TargetScan数据库对当归饮子有效成分、潜在靶点、PPI、KEGG、cross-talk及miRNA-mRNA机制进行预测分析。结果GSE57178差异分析得出257个差异基因,其中240个基因表达上调(如:HIF1A、MMP12、STAT3等);有17个基因表达下调(如:FABP7、KRT15、LGR5等),其中有36个当归饮子治疗慢性荨麻疹的潜在靶点,拓扑分析出24个关键靶点基因在其中发挥重要作用;cross-talk分析得出1个靶点(SELE)在TNF通路与细胞粘附分子(CAMs)2条通路中“串话”;1个靶点(ITGB2)在吞噬体与CAMs 2条通路中“串话”;2个靶点(CTSL、CTSS)在抗原处理表达、吞噬体与溶酶体3条通路中“串话”;2个靶点(VCAM1、ICAM1)在NF-kappa B、TNF与CAMs 3条通路中“串话”;1个靶点(TLR4)在HIF-1、NF-kappa B、吞噬体3条通路中“串话”;miRNA-mRNA预测分析得出24个潜在靶点mRNA,构成了477组miRNA-mRNA模式,在CU炎症反应中发挥作用。结论本研究从基因、分子角度预测和分析了当归饮子治疗CU的多靶点、多cross-talk、多miRNA-mRNA作用机制,为后续研究提供了依据,可成为未来机制研究的新方向。

Objective To explore the cross-talk and miRNA-mRNA mechanism of Danggui Yinzi in the treatment of chronic urticaria though using GEO chip combined with network pharmacology,so as to provide theoretical basis for follow-up experimental research.Methods The difference of GSE57178 chip was analyzed by R language limma package,and the effective components,potential targets,PPI,KEGG,cross-talk and miRNA-mRNA mechanism of Danggui Yinzi were predicted and analyzed by TCMSP,TCMID,PubChem,String,DAVID and TargetScan database.Results 257 differential genes were identified by GSE57178 differential analysis,of which 240 genes were up-regulated(such as HIF1A,MMP12,STAT3,etc.),17 genes were down-regulated(such as FABP7,KRT15,LGR5,etc.),among which 36 were potential targets for the treatment of chronic urticaria.Topological analysis showed that 24 key target genes played an important role.cross-talk analysis showed that one target(SELE)“cross talk”in the two pathways of TNF pathway and cell adhesion molecule(CAMs),one target(ITGB2)“crosstalk”in the two pathways of phagosome and CAMs,two targets(CTSL and CTSS)“cross talk”in the three pathways of antigen treatment expression,phagosome and lysosome,and two targets(VCAM1,ICAM1)“cross talk”in NF-kappaB,TNF and CAMs.One target(TLR4)“cross talk”in the three pathways of HIF-1,NF-kappaB and phagosome,and miRNA-mRNA predictive analysis showed that 24 potential targets mRNA,formed a 477 group of miRNA-mRNA patterns,which played a role in the inflammatory response of CU.Conclusion This study predicts and analyzes the multi-target,multi-cross-talk and multi-miRNA-mRNA mechanism of Danggui Yinzi in the treatment of CU from the genetic and molecular point of view,which provides a basis for follow-up research and can become a new direction of mechanism research in the future.