Bioinformatics Analysis Of Key Genes In Nephrotic Syndrome And Expression And Significance Of FK506-binding Protein 51 In Renal Tissues From Children With Nephrotic Syndrome

Part I:Bioinformatics analysis of differentially expressed genes in nephrotic syndromeObjective: Exploring key genes involved in the development of nephrotic syndrome(NS),differentially expressed genes(DEGs)were explored in NS using bioinformatics methods.Methods: The keyword "nephrotic syndrome" was searched in the Gene Expression Omnibus(GEO)database,and the related chip data were downloaded.The limmar package in R software was used to process the original data,and genes with a threshold P < 0.05 and fold change > 1.5 were screened as DEGs.The intersections of DEGs were analyzed with a Venn diagram analysis.We analyzed all the DEGs by Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and protein-protein interaction(PPI)network analyses.Results: Three GEO datasets were filtered,namely GSE104948,GSE104954,and GSE108113,from which 160,120,and 160 DEGs,respectively,were extracted.Seven cross-expressed genes were identified via the Venn diagram analysis: TIPARP,ZBTB16,ALB,PDK4,FOS,FKBP5,and HBB.The GO enrichment analysis suggested these genes were related to organelle cavities,drug binding(i.e.,macrolides and FK506),cell response to stimulation,and the regulation of cell death.The KEGG enrichment analysis indicated that these genes were mainly distributed in the estrogen signaling,cancer,B cell receptor signaling,and prolactin signaling pathways.Combining multiple analyses,FOS,FKBP5,and ALB were chosen as key genes.Conclusion: Fos proto-oncogene(Fos),ALB gene and FKBP5 gene were identifiedas key genes related to nephrotic syndrome.Part II: The expression and significance of FK506-binding protein 51 in renal tissue from children with nephrotic syndromeObjective: The purpose of this study was to assess the differential expression of the FKBP51 protein between nephrotic syndrome(NS)and control group kidney tissues through immunohistochemistry and to analyze its clinical significance.Methods: Eighteen children with primary nephrotic syndrome were selected for the study(NS group),and six samples of paracancerous kidney tissue were selected as controls.According to the pathological types,the NS group was divided into Minimal Change Disease(MCD)group(9 cases)and Focal Segmental Glomerular Sclerosis(FSGS)group(9 cases).According to clinical manifestations,the NS cases were also divided into simple-type group(8 cases)and nephritis-type group(10 cases).According to the effect of steroid therapy,the NS cases were classified into steroid-resistant group(10 cases)and non-steroid resistant group(8 cases).Clinical data on patient's age of onset,age upon percutaneous renal biopsy,24-hour urinary protein quantity,serum albumin,estimated glomerular filtration rate(e GFR),blood urea nitrogen,plasma total cholesterol,high-density lipoproteins,low-density lipoproteins,triglycerides,and renal pathology were collected for the NS cases.The expression levels of FKBP51 protein in kidney tissue from the NS and control groups were evaluated by immunohistochemistry.The results were then analyzed in combination with the clinical data and the group divisions given above.Results:1.FKBP51 was expressed in glomeruli,renal tubules,medulla,and nucleus and cytoplasm in both NS and control tissue samples.2.Compared to controls,the expression levels of FKBP51 protein in glomeruli in NS each group were increased(all P<0.05).3.The expression in the glomerular nucleus in NS cases or in the MCD or simple-type group was significantly higher than that in renal tubule nucleus(all P < 0.05).The expression in renal tubule cytoplasm in the NS cases or in MCD or FSGS or simple-type or nephritis-type or non-steroid resistant group was significantly higherthan that in glomerular cytoplasm(all P < 0.05).4.The expression of FKBP51 protein in distal tubules was significantly higher than that in proximal tubules in NS cases or in the FSGS or nephritis-type group(all P <0.05).5.The expression level of FKBP51 in renal tissues was positively correlated with the age of onset(r=0.488,P =0.040).Conclusion:1.FKBP51 protein was expressed in glomeruli and tubules in both NS and control and control tissue samples.The expression of FKBP51 protein was up-regulated in nephrotic syndrome.The expression of FKBP51 protein in the glomerular nucleus in NS cases or in the MCD or simple-type group was significantly higher than that in renal tubule nucleus.The expression in renal tubule cytoplasm in the NS cases or in MCD or FSGS or simple-type or nephritis-type or non-steroid resistant group was significantly higher than that in glomerular cytoplasm.2.The expression of FKBP51 protein in distal tubules was significantly higher than that in proximal tubules in NS cases or in the FSGS or nephritis-type group.3.The expression level of FKBP51 in renal tissues was positively correlated with the age of onset.