Comprehensive analysis of differentially expressed miRNAs in mice with kidney injury induced by chronic intermittent hypoxia

Abstract

Background: miRNAs have been reported to participate in various diseases. Nevertheless, the expression patterns of miRNA in obstructive sleep apnea (OSA)-induced kidney injury remain poorly characterized. In the current study, miRNA sequencing (miRNA-seq) was conducted to investigate miRNA expression profiles in a chronic intermittent hypoxia (CIH)-induced renal injury mouse model. Methods: The mouse model of chronic intermittent hypoxia was established. Differentially expressed miRNAs (DEmiRs) were detected using miRNA-seq technology. The sequencing data were subjected to Gene Ontology (GO) functional enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using a bioinformatics approach. RT-qPCR was further used to evaluate the sequencing results. Finally, we created a network for clarifying the relationship between the miRNAs and target genes. Results: In total, nine miRNAs were identified to be upregulated and nine to be downregulated in a mouse model of renal injury induced by chronic intermittent hypoxia. The Kyoto Encyclopedia of Genes and Genomes analyses revealed that the Wnt signaling pathway was involved in the development of chronic intermittent hypoxia-induced renal injury. Subsequently, eight DEmiRs, namely, mmu-miR-486b–3p, mmu-miR-215–5p, mmu-miR-212–3p, mmu-miR-344–3p, mmu-miR-181b-1-3p, mmu-miR-467a–3p, mmu-miR-467 d-3p, and mmu-miR-96–5p, showed a similar trend of expression when verified using RT-qPCR. Finally, five selected DEmiRs were used to construct a miRNA–mRNA network. Conclusion: In conclusion, a total of 18 DEmiRs were identified in the mouse model of chronic intermittent hypoxia-induced renal injury. These findings advance our understanding of the molecular regulatory mechanisms underlying the pathophysiology of obstructive sleep apnea-associated chronic kidney disease.