Expression Profile of Urinary Exosomal miRNAs in Patients With Diabetic Kidney Disease and Their Association With Kidney Damage.

Abstract

Purpose: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The aim of this study is to identify noninvasive biomarkers for early-stage DKD or targets for DKD treatment through the analysis of urinary exosomal miRNA 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). 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. Human podocytes and renal tubular epithelial cells (TECs) were treated with DKD-Exo to investigate the effects of DKD-Exo on podocyte apoptosis and the epithelial-mesenchymal transition (EMT) of TECs. Results: A total of 40 miRNAs were found to be differentially downregulated, 17 of which were named and 23 were untitled; miR-371a-3p, miR-371a-5p, miR-1260b, miR-222-3p, miR-1224-5p, and miR-1253 were reported in DKD for the first time. GO and KEGG pathway analyses suggest that these target genes are related to cellular apoptosis and renal fibrosis in DKD, and are involved in 135 pathways. In vitro, DKD-Exo induced the apoptosis of podocytes and collagen synthesis in TECs. 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.