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.
Highlights
Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic complication that frequently develops after cardiac catheterization procedures involving the administration of iodinated contrast media (CM)
The average elevation of serum creatinine (SCr) was (59.9 ± 23.0) % over baseline in the CI-AKI rats, compared with (-10.5 ± 17.1) % in the control rats injected with normal saline (Table 1, P < 0.05)
Pronounced histopathological alterations in the tubular epithelial cells of the inner and outer medulla were observed in the CI-AKI rats, including vacuole-like denaturation, nucleus pyknosis, and apoptotic body formation (Fig 1A)
Summary
Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic complication that frequently develops after cardiac catheterization procedures involving the administration of iodinated contrast media (CM). CI-AKI has emerged as one of the most important causes of hospitalacquired acute renal failure, accounting for 10–25% of all cases [1,2,3]. The onset of CI-AKI is significantly associated with adverse events, including increased mortality and a long-term decline in kidney function [4,5,6]. Despite advances in the introduction of safer CM and the optimized of hydration protocols, CM continues to pose a substantial threat of CI-AKI in vulnerable renal patients [7]. Research has identified several potential routes for the pathogenesis of CI-AKI, including direct cytotoxic effects, medullary hypoxia, and the perturbation of renal tubulodynamics [8]. The precise molecular pathways remain poorly understood, resulting in the absence of specific preventive strategies or sensitive biomarkers for early diagnosis
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