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.

Circ_0047339 promotes the activation of fibroblasts and affects the development of urethral stricture by targeting the miR-4691-5p/TSP-1 axis

“…At present, there are few research articles on the relationship between circRNA and urethral stricture. The existing literature mainly focuses on renal fibrosis 20 , 27 . Other studies have found that circRNA is related to the mechanism of keloid formation 29 – 31 .…”

“…Circular RNA (circRNA) is a new endogenous non-coding RNA that has attracted research interest 19 . Previous studies show that circRNA is involved in many disease processes, including renal and liver fibrosis 20 , 21 . In the reports of fibrosis-related diseases, like myocardial fibrosis 22 , diabetic nephropathy 23 and pulmonary fibrosis 24 , it has been revealed that circRNA acts as a molecular sponge, which can isolate miRNA molecules and prevent the mechanism of targeting mRNA.…”

Renal-Protective Roles of Lipoic Acid in Kidney Disease

“…This model has certain advantages in that it is a nonuremic normotensive disorder in the absence of any apparent inflammatory or toxic insult to the kidneys [ 88 ]. Moreover, the UUO model of kidney injury is also a good model for studying the pathophysiology of renal fibrosis [ 89 , 90 , 91 , 92 , 93 ]. Therefore, the UUO model of kidney injury may closely mimic the underlying pathophysiology of human obstructive kidney injury [ 94 , 95 ].…”

Circular RNAs in Acute Kidney Injury: Roles in Pathophysiology and Implications for Clinical Management

“…These findings mirror those in other mammalian models, with 605 circRNAs upregulated and 745 circRNAs downregulated in a murine UUO model. Gene Ontology analysis showed that many of these circRNAs were involved in pathways relating to cell apoptosis and p53 signalling [ 96 ]. In a smaller study, mmu_circ_30032 expression was upregulated in the murine UUO model, promoted by the activation of the p38-MAPK pathway, resulting in the deposition of type I collagen, type III collagen, and fibronectin via miR-96-5p [ 57 ].…”