Potential role of upregulated microRNA-146b and −21 in renal fibrosis

The aim of the present study was to identify candidate microRNAs (miRNAs) involved in the progression of renal fibrosis. Dataset GSE42716 of miRNAs extracted from kidneys from mice with unilateral ureteral obstruction (UUO), and mice without UUO was downloaded from the Gene Expression Omnibus database. The Limma package was used to identify differential expression between mice with and without UUO. Renal disease-related miRNAs were predicted based on the miRWalk database. Thereafter, candidate miRNAs were screened by taking the intersection of differentially expressed miRNAs and predicted miRNAs, followed by screening of target genes using miRWalk and transcription factors using the TransmiR database. An integrative regulatory network was constructed using Cytoscape software. Enrichment analysis of target genes was also performed. In total, 76 differentially expressed miRNAs were identified in kidneys with UUO compared with the normal samples based on dataset and 9 miRNAs were identified as related to renal disease from the miRWalk database. A Venn diagram revealed two overlapping upregulated miRNAs; miR-146b and miR-21. Transcription factor NFKB1 may activate miR-146b and AKT may activate miR-21. In addition, miR-21 had a regulatory effect on IFNG expression and miR-146b may regulate the expression of BCL2, PTEN and IFNG. Furthermore, target genes of miR-146b and miR-21 were significantly enriched in 14 Gene Ontology terms including regulation of cell proliferation (e.g., BCL2, PTEN and IFNG). Overexpression of miR-21 may be activated by AKT2 and contribute to renal fibrosis by negatively regulating IFNG expression. Furthermore, miR-146b may be activated by NFKB1 and subsequently reduce the expression of BCL2, PTEN and IFNG in the progression of renal fibrosis.