Bioinformatics Analysis Of Urinary Exosomal MiRNAs In Idiopathic Membranous Nephropathy

Background and Objective: Idiopathic membranous nephropathy(IMN)is the leading cause of nephrotic syndrome in adults,and there is an urgent need for reliable non-invasive biomarkers for disease diagnosis and efficacy monitoring.Currently,several biomarkers for example: phospholipase A2 receptor 1(PLA2R1),type 1thrombospondin 7A domain(THSD7A)and Nel-like protein 1(NELL-1),have been found to be associated with idiopathic membranous nephropathy(IMN)disease progression.In this study expects to further understand the pathogenesis of IMN through the comprehensive analysis of urinary exosomal miRNAs in patients with IMN,so as to further guide the diagnosis and treatment of the disease.Methods: In this study,we screened six IMN patients based on the results of renal biopsy,and recruited five healthy people as a control group,collecting urine samples from both groups and extracting exosomes.High-throughput sequencing was used to the miRNA profiles of urinary exosomes from IMN patients and healthy controls(CON).Thereafter we performed bioinformatics analysis based on the sequencing results to designed an mRNA-miRNA regulatory network for further IMN pathogenesis.Results: 1.A total of 11 people were screened in this study and divided into two groups: the IMN group(6 people)and the control group(5 people).All IMN patients were identified based on a PLA2 R testing and renal biopsy.Compared with the control group,24-hour proteinuria was significantly higher and serum albumin was significantly lower in the IMN group(both p < 0.001).2.Through high-throughput sequencing of exosomes extracted from urine,we screened 131 differentially expressed miRNAs,including 28 specifically expressed miRNAs.3.A regulatory network consisting of 139 key genes and 228 miRNA-mRNA pairs was constructed by using the GSE115857 dataset of the GEO database and the differentially expressed miRNAs obtained through screening,and the network was comprehensively analyzed.4.Finally,two miRNA-mRNA pairs,miR-155-5p-FOS and miR-146a-5p-BTG2,were found to be differentially expressed in IMN,and these findings may provide more accurate diagnostic and therapeutic targets for IMN.Conclusion: Our findings demonstrate for the first time that there are significant differences in miRNAs in urinary exosomes between IMN patients and healthy controls.And based on the results we constructed a miRNA-mRNA regulatory network,through comprehensive analysis of the regulatory network,we found that two miRNA-mRNA pairs,miR-155-5p-FOS and miR-146a-5p-BTG2,were differentially expressed in IMN,these The findings may provide more accurate diagnostic and therapeutic targets for IMN.