Differential expression analysis of urinary exosomal circular RNAs in patients with IgA nephropathy

Aims Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease to cause end‐stage kidney disease. This study investigated the difference in urinary exosomal circular RNA (circRNA) expression profiles between patients with IgAN and healthy controls (HCs), for better understanding of gene regulation in exosomes of IgAN patients. Methods A pairwise comparison of urinary circRNA expression profiles between IgAN patients and HCs was performed using methods, including high‐throughput sequencing and quantitative polymerase chain reaction. Moreover, the potential functions of differentially expressed circRNAs (DECs) in IgAN were investigated by gene ontology (GO) enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; and the circRNA‐miRNA‐mRNA network. Results We identified 450 upregulated and 26 downregulated circRNAs in the IgAN patients. GO analysis showed that these enriched circRNAs might regulate primary miRNA processing, the ability of angiotensin receptor binding, and stress fibre function. KEGG analysis suggested these DECs may be closely associated with the phosphoinositide‐3‐kinase‐protein kinase B/Akt (PI3K‐Akt) signalling pathways. Network analysis revealed the relationship between circRNAs and their target genes. Conclusion The identified DECs may be useful for both researches on molecular aetiology of IgAN and development of potentially novel non‐invasive biomarkers of IgAN. SUMMARY AT A GLANCE An RNA‐sequence analysis of RNAs in urinary exosomes identified a number of differentially expressed circular RNAs in immunoglobulin A nephropathy (IgAN) patients as compared to healthy controls. These circRNAs are associated with the regulation of pathways relevant to IgAN and may provide useful non‐invasive biomarkers for this condition.