Identification of circular RNA expression profiles in renal fibrosis induced by obstructive injury.

ABSTRACT

INTRODUCTION: Advancing renal fibrosis is the common histopathological feature of chronic obstructive nephropathy, representing the final pathway of nearly all chronic and progressive nephropathies. Increasing evidences suggest that circular RNAs (circRNAs) are crucial regulatory molecules present at virtually every level of the cellular pathophysiological process. Nonetheless, there are a few evidences for the role of circRNAs in renal fibrosis induced by obstructive nephropathy. AIMS: We performed RNA-seq analysis to analyze the expression profiles of circRNAs in the obstructed kidneys to identify the potential circRNAs and their network. METHODS: With silk ligated the left ureter to establish a mice unilateral ureteral obstruction (UUO) model. Renal tissue circRNAs were obtained and were screened by a circRNA microarray. The circRNA-miRNA-mRNA regulatory network and the target genes were visualized using Cytoscape software. RESULTS: The microarray results showed that 5454 and 2935 circRNAs were detected in the control and UUO group, respectively. There were 605 circRNAs up-regulated and 745 circRNAs down-regulated in the obstructive kidneys. The top 5 up-regulated and down-regulated circRNAs were chosen for predicting the circRNA/miRNA/target mRNAs triple network. The GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these circRNAs and the triple network were enriched in the process of apoptosis, p53 signaling pathway, cell growth and cell death, which might participate in the pathogenesis of obstructive nephrology. CONCLUSION: Our results show that the dis-regulated circRNAs might play crucial roles in the pathogenesis of obstructive nephropathy, which proceeds to identify novel therapeutic targets for chronic kidney disease.