Differential expression of circRNA in renal ischemia-reperfusion injury and its effect on Hippo signaling pathway / 中华急诊医学杂志

ABSTRACT

Objective:To analyze the differential expression profile of circRNA and the expression changes of Hippo signaling molecule YAP in renal ischemia-reperfusion injury of mice.Methods:A model of renal IR damage in mice was induced, and serum creatinine (Scr) and urea nitrogen (BUN) concentrations and histological changes of samples were detected to assess renal function and tubular injury. Illumina HiSeq 2500 system was used for high-throughput paired-end sequencing to establish the circRNA expression profile with significant differential expression. Real-time quantitative polymerase chain reaction (qRT-PCR) verified the sequencing results and detected related genes. Gene function (GO) and pathway (KEGG) analysis were performed to predict the biological processes and the major signal pathways involved by differentially expressed circRNAs. The expression level of the main signaling molecule was examined by western blot.Results:Twenty-one distinctly differentially expressed circRNAs ( fold change ≥ 2) were found in IR 24 h kidney tissues compared with the expression in the control groups ( P < 0.05), among which 10 circRNAs were observed to be up-regulated and 11 down-regulated. CircRNA.1100 and circRNA.1122 were randomly (random number) selected for verification by qRT-PCR, and the relative expressions after renal IR 1day were decreased by (0.23±0.016) and (0.36±0.12), respectively, which were highly consistent with the sequencing trends. Analysis of biological functions and pathways showed that differential expression circRNA was significantly enriched in cell cycles, division, growth, apoptosis, death, and Hippo signaling pathways. The Hippo pathway effector molecule YAP protein was significantly up-regulated after renal IR 1day and until the 3rd day of IR. Conclusions:CircRNA may be involved in the regulation of renal IR injury. CircRNA and Hippo pathway may play a key role in the development of renal IR injury.