Co-expression analysis reveals dysregulated miRNAs and miRNA-mRNA interactions in the development of contrast-induced acute kidney injury

Abstract

The pathogenesis of contrast-induced acute kidney injury (CI-AKI) is incompletely understood. MicroRNAs (miRNAs) are important mediators that normally function via post-transcriptional degradation of target mRNAs. Emerging evidence indicates the appearance of differentially expressed (DE) miRNAs in CI-AKI following the injection of intravenous contrast medium. However, there are differences in the pathological mechanism and incidence of CI-AKI between intravenous and intra-arterial contrast administration. The present study aimed to investigate the critical roles of dysregulated miRNAs and their associated mRNAs in kidney injury following intra-arterial contrast medium exposure. Based on a reliable CI-AKI rat model, we conducted genome-wide miRNA and mRNA expression profiling analysis using deep sequencing. In the study, 36 DE mature miRNAs were identified (fold change > 1.5 and p value < 0.05) in the kidneys of CI-AKI rats (n = 3) compared with that in the controls (n = 3), consisting of 23 up-regulated and 13 down-regulated DE miRNAs. Bioinformatic analysis revealed that wingnut (Wnt), transforming growth factor beta (TGF-β), and 5'-AMP-activated protein kinase (AMPK) signaling pathways were most likely to be modulated by these dysregulated miRNAs. Around 453 dysregulated genes (fold change > 2.0 and p value < 0.05) were identified. Integrated analysis revealed 2037 putative miRNA-mRNA pairs with negative correlations. Among them, 6 DE miRNAs and 13 genes were selected for further quantitative real-time reverse transcription polymerase chain reaction validation (n = 6 for each group), and a good correspondence between the two techniques was observed. In conclusion, the present study provided evidence of miRNA-mRNA interactions in the development of kidney injury following an intra-arterial contrast injection. These findings provide insights into the underlying mechanisms of CI-AKI.