Abstract
Background MicroRNAs (miRNAs) are confirmed to participate in occurrence, development, and prevention of membranous nephropathy (MN), but their mechanism of action is unclear. Objective With the GEO database and the use of bioinformatics, miRNA-mRNA regulatory network genes relevant to MN were explored and their potential mechanism of action was explained. Methods The MN-related miRNA chip data set (GSE51674) and mRNA chip data set (GSE108109) were downloaded from the GEO database. Differential analysis was performed using the GEO2R online tool. TargetScan, miRTarBase, and StarBase databases were used to predict potential downstream target genes regulated by differentially expressed miRNAs, and the intersection with differential genes were taken to obtain candidate target genes. According to the regulatory relationship between miRNA and mRNA, the miRNA-mRNA relationship pair was clarified and Cytoscape was used to construct a miRNA-mRNA regulatory network. WebGestalt was used to conduct enrichment analysis of the biological process of differential mRNAs in the regulatory network; FunRich analyzes the differential mRNA pathways in the miRNA-mRNA regulatory network. And the STRING database was used to construct a PPI network for candidate target genes, and Cytoscape visually analyzes the PPI network. Results Experiments were conducted to screen differentially expressed miRNAs and mRNAs. There were 30 differentially expressed miRNAs, including 22 upregulated and 8 downregulated; and 1267 differentially expressed mRNAs, including 536 upregulated and 731 downregulated. Using TargetScan, miRTarBase, and StarBase databases to predict the downstream targets of differentially expressed miRNAs, 2957 downstream target genes coexisting in the 3 databases were predicted to intersect with differentially expressed mRNAs to obtain 175 candidate target genes. Finally, 36 miRNA-mRNA relationship pairs comprising 10 differentially expressed miRNAs and 27 differentially expressed mRNAs were screened out, and the regulatory network was constructed. Further analysis revealed that the miRNA regulatory network genes may be involved in the development of membranous nephropathy by mTOR, PDGFR-β, LKB1, and VEGF/VEGFR signaling pathways. Conclusion The miRNA regulatory network genes may participate in the regulation of podocyte autophagy, lipid metabolism, and renal fibrosis through mTOR, PDGFR-β, LKB1, and VEGF/VEGFR signaling pathways, thereby affecting the occurrence and development of membranous nephropathy.
Highlights
Membranous nephropathy (MN) is a common pathological type of adult nephrotic syndrome
MN accounts for about 20% to 37% of adult nephrotic syndrome, and about 1/3 of patients eventually develop end-stage renal disease [1]. 75%–80% of MN are idiopathic membranous nephropathy (IMN), and 20%–25% are secondary membranous nephropathy or atypical membranous nephropathy
A single-center study in Beijing showed that, from 2003 to 2012, the incidence of IMN in primary glomerular disease increased from 16.8% to 29.35%, and the proportion of young patients suffering from early primary membranous nephropathy increased significantly [4]
Summary
Membranous nephropathy (MN) is a common pathological type of adult nephrotic syndrome. It was found that about 1/3 of patients with primary membranous nephropathy will be completely relieved naturally, while another 1/3 of patients will develop lifelong proteinuria while retaining kidney function for a long time, leaving 1/3 of patients will progress to end-stage renal disease [8]. With the GEO database and the use of bioinformatics, miRNA-mRNA regulatory network genes relevant to MN were explored and their potential mechanism of action was explained. Further analysis revealed that the miRNA regulatory network genes may be involved in the development of membranous nephropathy by mTOR, PDGFR-β, LKB1, and VEGF/VEGFR signaling pathways. E miRNA regulatory network genes may participate in the regulation of podocyte autophagy, lipid metabolism, and renal fibrosis through mTOR, PDGFR-β, LKB1, and VEGF/VEGFR signaling pathways, thereby affecting the occurrence and development of membranous nephropathy Conclusion. e miRNA regulatory network genes may participate in the regulation of podocyte autophagy, lipid metabolism, and renal fibrosis through mTOR, PDGFR-β, LKB1, and VEGF/VEGFR signaling pathways, thereby affecting the occurrence and development of membranous nephropathy
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