Bioinformatic analysis to explore key genes associated with brain ischemia–reperfusion injury in rats

Abstract

<b>Objectives:</b> Ischemia-reperfusion (I/R) injury can aggravate the dysfunction and structural damage of tissues and organs. This study aimed at investigating the pathogenesis of I/R injury. <b>Methods:</b> GSE82146 was extracted from Gene Expression Omnibus database, which included 12 nonischemic control (NIC) hippocampal tissues and 15 complete global brain ischemia (CGBI)-reperfusion hippocampal tissues. After processing the original data using the affy package, the differentially expressed genes (DEGs) between CGBI and NIC samples were analysed by the limma package. An enrichment analysis for the DEGs was implemented based on the MATHT online tool. Using Cytoscape software, a protein-protein interaction (PPI) network was built and significant network modules were obtained. Finally, miRNA-gene pairs were predicted using the miRWalk2.0 tool, and the miRNA-gene regulatory network was built using the Cytoscape software. <b>Results:</b> Overall, 322 DEGs (279 upregulated and 43 downregulated) were present in the CGBI samples. In PPI network, JUN, STAT3, ATF3, VEGFA and ATF4 had higher degrees. Four significant modules (modules a, b, c and d) were obtained from PPI network. Enrichment analysis suggested that <i>FGF2</i> in module d was involved in MAPK signalling pathway. In the miRNA-gene regulatory network, <i>rno-miR-125a-5p</i> and <i>rno-miR-125b-5p</i> were among the top 10 miRNAs. <b>Conclusion:</b> <i>JUN</i>, <i>STAT3</i>, <i>ATF3</i>, <i>VEGFA</i>, <i>ATF4</i>, <i>FGF2</i>, <i>rno-miR-125a-5p</i> and <i>rno-miR-125b-5p</i> might affect the development and progression of I/R injury.