Screening of genes related to immune response in postmenopausal osteoporosis and their target herbal components
Objective To identify genes related to immune response in postmenopausal osteoporosis by bioinformatics,and to investigate the mechanism of their action and screen the active ingredients of targeted traditional Chinese medicines.Methods Search for"postmenopausal osteoporosis"in the gene expression database(GEO),download the gene dataset GSE230665,and obtain the differentially expressed genes through the"limma"packet in R software.David tool was used to perform GO functional enrichment analysis for differential genes and screen out key genes related to immune response,and then GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for key genes.STRING platform and Cystoscope software were used to establish protein interaction(PPI)network,and MCODE and CytoNCA plug-ins were used to identify important gene cluster modules and core genes.Search for"postmenopausal osteoporosis"in CTD database to further screen core genes and search for TCM active ingredients targeting core genes,search for 3D structure of TCM active ingredients in PubChem database,and perform molecular docking with Autodock 4 software.And explore the interaction between core genes and postmenopausal osteoporosis.Results 43 Key genes were selected in postmenopausal osteoporosis,and GO enrichment analysis showed that they were mainly involved in the positive regulation of inflammatory response,the production of IL-12,tumor necrosis factor,cell migration and chemotaxis.KEGG pathway mainly involves chemokine signaling pathway,PI3K/Akt signaling pathway,TNF signaling pathway,NF-κB signaling pathway,etc.9 Core genes were identified as IL-10,B2M,IL-17A,CXCR4,TLR4,CCR5,NOTCH1,TLR2,and SMAD3.It was verified that the expression of core genes was up-regulated in postmenopausal osteoporosis patients.Estradiol,resveratrol,quercetin,curcumin,bisphenol A,and lignans showed high interaction indices with the core genes,and the active ingredients of these herbal medicines may repair postmenopausal osteoporosis by suppressing the immune response.Conlusion Bioinformatics was utilized to screen the core genes associated with immune response(IL-10,B2M,IL-17A,CXCR4,TLR4,CCR5,NOTCH1,TLR2,SMAD3)as well as their main TCM active ingredients(estradiol,resveratrol,quercetin,curcumin,bisphenol A,and lignoflavone)subject to targeted regulation,which will provide a new theoretical basis for further exploring the molecular pathogenesis as well as new therapeutic targets of postmenopausal osteoporosis.
bioinformaticspostmenopausal osteoporosisbone immunologycore genesestradiolresveratrolcurcumin,bisphenol A
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