Discovery Based On Bioinformatics That Inhibiting The Focal Adhesion Signaling Pathway May Be A New Strategy For The Treatment Of Focal Segmental Glomerulonephritis

Objective:To explore the new pathogenesis of focal segmental glomerulonephritis(FSGS),in order to provide a new treatment strategy for the clinical treatment of FSGS.Methods:Download the gene expression profiling datasets GSE129973 and GSE121233 of FSGS renal puncture specimens from the GEO database.There are a total of 50 samples,including 25 FSGS renal puncture samples and 25 normal kidney tissue samples.Use the R software for data collection and use the limma package in R for differential expression analysis.After obtaining the DEGs,search for the protein-protein interaction(PPI)of the encoding protein in the STRING database,and use Cytoscape to map the PPI network diagram to select the hub gene of FSGS through the Cytohubba plug-in.Use the DAVID database to perform GO function enrichment analysis and KEGG signal pathway enrichment analysis for differential genes,and determine the main signal pathways involved in the hub gene.Then use the GSEA software to perform KEGG pathway analysis on the whole gene expression profile data of all sample data to verify whether the signal pathway involved in the hub gene is consistent with the analysis results of the DAVID database.Finally,the potential mechanism of the occurrence and development of FSGS is analyzed based on literature reports.Results:A total of 151 DEGs were screened out by the differential analysis of the limma package,including 50 up-regulated genes and 101 down-regulated genes.After obtaining the PPI results of DEGs in the STRING database,the Cytohubba plug-in of Cytoscape was used to screen FSGS-related hub genes,and a total of 7 genes(ALB,FN1,EGF,SPP1,IGF1,PTGS2,FOS)were screened,among which the expression of FN1 and SPP1 was up-regulated,ALB,EGF,IGF1,PTGS2,and FOS were down-regulated.In the DAVID database,GO enrichment analysis was performed from biological processes(BP),molecular functions(MF),and cellular components(CC).The results showed that BP terms of the DEGs were signifcantly enriched in response to wounding?response to lipopolysaccharide?platelet deranulation?cellular oxidant detoxification ?inflammatory response?immune response?innate immune response?cell adhesion?extracellular matrix organization?angiogenesis.The MF terms were mainly enriched in calcium ion binding?heme binding?heme binding?oxygen binding?integrin binding?heparin binding?RAGE receptor binding?peroxidase activity?glutathione transferase activity?haptoglobin binding.The CC terms were mainly enriched in extracellular exosome?blood microparticle?platelet alpha granule lumen?Golgi lumen?haptoglobin-hemoglobin complex?hemoglobin complex.KEGG pathway analysis revealed that the DEGs were mainly enriched in Focal adhesion?Toll-like receptor signaling pathway?TNF signaling pathway?AMPK signaling pathway?PI3K-Akt signaling pathway?Drug metabolism-cytochrome P450?Chemical carcinogenesis?Glutathione metabolism?Pathways in cancer.GSEA enrichment analysis verified that the Focal adhesion signaling pathway was not only significantly enriched in DEGs,but also significantly enriched in all genes,and 4 key genes(FN1,SPP1?EGF?IGF1)were obtained.Conclusion:FN1,SPP1,EGF and IGF1 are key genes that participate in the occurrence and development of FSGS through the Focal adhesion signaling pathway.This means that inhibiting the Focal adhesion signaling pathway may be a new strategy for the treatment of FSGS.