Analysis of Differentially Expressed Long Noncoding RNA in Renal Ischemia-Reperfusion Injury

Abstract

Background: Renal ischemia-reperfusion (IR) injury is one of the major causes of acute renal failure which seriously endangers the health and life of patients. Currently, there is still lack of comprehensive knowledge of the molecular mechanism of renal IR injury, and the regulatory role of long noncoding RNA (lncRNA) in renal IR damage remains poorly understood.

Aim: The aim of this study was to analyze the expression spectrum of lncRNA in renal IR damage in mice and to explore specific lncRNA that may be involved in regulating the development of human renal IR injury.

Methods: RNA-Seq was used to investigate the lncRNA profile of renal IR injury in a mouse model, and conservation analysis was performed on mouse lncRNAs with differential expression (fragments per kilobase of transcript per million mapped reads ≥2) by BLASTN. The potential functions and associated pathways of the differentially expressed lncRNA were explored by bioinformatics analysis. The cell hypoxia model was used to detect the expression of the candidate lncRNA.

Results: Of the 45,923 lncRNA transcripts detected in the samples, and 5,868 lncRNAs were found to be significantly differentially expressed (p < 0.05 and fold change ≥ 2) in 24-h IR kidney tissue compared to the expression in the control group. It was found that 56 differently expressed mouse lncRNA transcripts have human homology by analyzing the conserved sequences. We also found that lncRNA-NONHSAT183385.1 expression significantly increased in HK2 cells after 24 h of hypoxia and increased further 6 h after reoxygenation, and after 24 h of reoxygenation it was dramatically downregulated, indicating that NONHSAT183385.1 may be involved in the pathophysiological process of renal tubular epithelial cells in response to ischemia in human renal IR.

Conclusion: Our study revealed differentially expressed lncRNAs in renal IR damage in mice and identified a set of conserved lncRNAs, which would help to explore lncRNAs that may play important regulatory roles in human renal IR injury.

Keywords: Long noncoding RNA; RNA sequencing; Renal ischemia-reperfusion injury.