Circular RNA involved in the protective effect of losartan on ischemia and reperfusion induced acute kidney injury in rat model

摘要

Although losartan has inhibitory effects on acute kidney injury (AKI), the underlying molecular mechanisms have remained largely unclear. The expressional alteration of circular RNAs (circRNAs) was investigated in the present study to understand the therapeutic effects of losartan against AKI. AKI rat models were established by ischemia and reperfusion (I/R) treatment. Urea and creatinine levels were determined and histological features of kidney tissues examined following hematoxylin and eosin staining. Cell apoptosis was assessed by TUNEL. CircRNA profiles were obtained by RNA-Seq followed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Expression of circRNAs was validated by quantitative RT-PCR. I/R treatment induced an increase in plasma urea and creatinine levels, abnormal kidney tubular structure, and cell apoptosis in Sprague-Dawley (SD) rats, which were effectively inhibited by pre-treatment with losartan. Further RNA-Seq analysis revealed a wide range of differentially expressed circRNAs in I/R rat kidneys, which were reversed by losartan pre-treatment. GO and KEGG analyses revealed that the circRNAs are associated with various biological processes, including the PI3K-Akt signaling pathway. Specifically, circ-Dnmt3a, circ-Akt3, circ-Plekha7, and circ-Me1 were down-regulated in AKI rats and restored by losartan. The current study provides an overview of circRNAs expression profiles based on the inhibitory effects of losartan in ischemic AKI rats.