Expression profile of urinary exosomal miRNAs in patients with diabetic kidney disease and their associated with kidney damage

Abstract

Purpose Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The aim of study is to seek noninvasive biomarkers for DKD at early stage or a target for the treatment of DKD through analysis of the urinary exosomal miRNAs expression profiles in DKD patients. Methods The urinary exosomes were isolated from type 2 diabetes (T2DM) patients with DKD confirmed by renal biopsy (DKD-Exo). Treatment of human podocytes and renal tubular epithelial cells (TECs) with DKD-Exo to observe the effects of DKD-Exo on podocyte apoptosis and epithelial-mesenchymal transition (EMT) of TECs. The urinary exosomal miRNAs expression profiles were detected using miRNA sequencing, and differentially expressed miRNAs were verified by real-time quantitative PCR. Target genes of these miRNAs and relevant pathways in DKD were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Results DKD-Exo induced the apoptosis of podocytes and EMT of TECs. A total of 40 differentially downregulated miRNAs were found, 17 of all were named and 23 were newly discovered, some differentially expressed miRNAs in DKD patients were reported for the first time. GO and KEGG pathway analysis suggest that these target genes were related to biological processes, molecular function and cellular component, and involved in 135 pathways. Conclusion Our study implies that the urinary DKD-Exo could deliver biological information to podocytes or TECs, which play an important role in pathogenesis of DKD.