Mechanism of Intestinal Metaplasia of Gastric Mucosa and Prediction of Traditional Chinese Medicine Based on M2 Polarization of Macrophages
Objective To explore the effect of M2 polarization of macrophages on intestinal metaplasia(IM)of gastric mucosa and its therapeutic target,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The data sets related to IM and macrophage M2 polarization were downloaded from the public database,and the correlation between IM and macrophage M2 polarization was further expounded by immune infiltration analysis,gene correlation analysis,functional enrichment analysis,protein interaction network and experimental verification.Finally,the obtained hub genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and treatment of IM.Results Immunoinfiltration and immunofluorescence analysis showed that the expression of macrophage M2 polarization markers CD68+CD163+(P=0.0394)and CD68+CD206+(P=0.002)in IM group was significantly higher than that in normal group,and the infiltration level of M2 macrophages in IM group was significantly higher than that in normal group(P＜0.05).IM related marker genes(CDX1,MUC2,TFF3)were positively correlated with macrophage M2 polarization markers(CD209,ARG1,MSR1,STAT3,IL32,SELENOP)(P＜0.05).Functional enrichment analysis showed that the differential genes co-expressed by IM and macrophage M2 polarization were closely related to molecular biological functions such as carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.Finally,7 pivotal differential genes co-expressed by IM and macrophage M2 were screened,which were TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA,respectively.According to the prediction of traditional Chinese medicine,23 kinds of traditional Chinese medicine for IM were predicted,which could be classified into 14 categories according to their efficacy,among which heat-clearing antidote appeared most frequently,followed by drugs for tonifying qi and painkillers for promoting blood circulation drugs.Conclusion Macrophage M2 polarization may be involved in the pathogenesis and development of IM through exocrine pathway.IM and seven hub genes co-expressed by macrophage M2 polarization(TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA)and IM specific molecules CDX1,MUC2 and TFF3 may be associated with each other and participate in the progression of IM.The therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM in traditional Chinese medicine.Starting from the M2 polarization of macrophages,it is expected to become a new direction and breakthrough in clinical prevention and treatment of IM.
Intestinal metaplasiaMacrophage M2 polarizationDifferentially expressed genesBioinformaticsPrediction of traditional Chinese medicineTherapeutic method of Jianpi Huayu Jiedu
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