Dysregulation of renal microRNA expression after deep hypothermic circulatory arrest in rats

Acute kidney injury (AKI) is a severe complication of cardiopulmonary bypass-deep hypothermic circulatory arrest (DHCA) surgery. Non-coding microRNAs (miRNAs) are considered as key players in kidney physiology and pathology. However, whether they are implicated in DHCA-induced AKI at the early stage post-surgery is less studied, and requires for further investigation.

In this study, kidney tissues were removed at 2 h post-surgery from Sprague-Dawley rats that underwent a 60-min DHCA (18°C), with samples from sham-operated rats as control. Renal RNA isolates were analysed with Affymetrix miRNA microarray 4.0 containing 728 mature rat miRNA probes.

Seventy-one miRNAs were down-regulated and 4 were up-regulated in the kidneys of DHCA rats [log2 (fold change, FC) > 1, P < 0.05]. Novel differentially expressed miRNAs, such as miRNA-3068, miR-1949 and miR-3473, were identified in the injured kidney tissues. Putative target genes of the down-regulated miR-30b-5p, miR-199a-5p, miR-148b-3p and miR-10a-3p were subjected to analyses of gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results indicated that these miRNAs targeted a large set of genes involved in essential biological processes related to AKI pathogenesis, such as apoptotic process and response to hypoxia, as well as genes implicated in critical signalling pathways, such as chemokine, lysosome and FoxO signalling pathways (false discovery rate-corrected, P < 0.05).

The identified 75 differentially expressed miRNAs hold the potential to serve as novel early markers and novel therapeutic targets for DHCA-AKI.