1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
2. Division of Endocrinology, Department of Internal Medicine, Qilu Hospital of Shandong University, Jinan 250000, China.
3. Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
4. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
5. Key Laboratory of Organ Transplantation, Ministry of Education, Ministry of Public Health, Chinese Academy of Medical Sciences, Wuhan 430030, China.
6. Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, Wuhan 430030, China.
Introduction: Hepatic ischemia/reperfusion (I/R) injury is common after liver surgery, particularly in patients of older age. However, an understanding of the mechanism of injury remains incomplete. In this study, we explored the molecular mechanisms underlying hepatic I/R injury and associations with age in a murine model.
Methods: Gene expression profiling datasets (GSE72315 and GSE10654) and a microRNA (miRNA) expression profiling dataset (GSE72315) were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) and miRNAs (DEMiRs) were identified using online GEO2R or R before and after hepatic I/R injury in mice. Significant Gene Ontology (GO) terms were analyzed with the DAVID functional annotation tool. The DEMiR-miRNA target gene (miRTG) networks were constructed with miRTarBase, and the differentially expressed miRNAs and genes were analyzed with real-time quantitative polymerase chain reaction and immunofluorescence staining.
Results: Through bioinformatic analysis, seven novel candidate miRNAs were identified that may regulate the expression of nine genes in hepatic I/R injury. Before and after hepatic I/R injury, mmu-miR-9-5p, mmu-miR-329-3p, and mmu-miR-290a-5p showed significant differential expression both in young (1 month old) and old (1 year old) mice. miR-329-3p had the most significant differential expression, and its predicted target genes Adamts4 and Dnajb1 were also significantly upregulated.
Conclusions: The decrease in miR-329-3p expression upregulated Adamts4 and Dnajb1 expression in mouse hepatic I/R injury in an age-independent manner. This finding contributes to our understanding of hepatic I/R injury, and highlights novel molecular targets for future therapeutic development.
Keywords: Ischemia/reperfusion injury, liver surgery, microRNA, bioinformatics analysis, age-independent manner.