Abstract
Hypoxia preconditioning is an effective strategy of intrinsic cell protection. An acute repetitive hypoxic mice model was developed. High-throughput microarray analysis was performed to explore the integrative alterations of gene expression in repetitive hypoxic mice. Data obtained was analyzed via multiple bioinformatics approaches to identify the hub genes, pathways and biological processes related to hypoxia preconditioning. The current study, for the first time, provides insights into the gene expression profiles in repetitive hypoxic mice. It was found that a total of 1175 genes expressed differentially between the hypoxic mice and normal mice. Overall, 113 significantly up-regulated and 138 significantly down-regulated functions were identified from the differentially expressed genes in repetitive hypoxic brains. Among them, at least fourteen of these genes were very associated with hypoxia preconditioning. The change trends of these genes were validated by reverse-transcription polymerase chain reaction and were found to be consistent with the microarray data. Combined the results of pathway and gene co-expression networks, we defined Plcb1, Cacna2d1, Atp2b4, Grin2a, Grin2b and Glra1 as the main hub genes tightly related with hypoxia preconditioning. The differential functions mainly included the mitogen-activated protein kinase pathway and ion or neurotransmitter transport. The multiple reactions in cell could be initiated by activating MAPK pathway to prevent hypoxia damage. Plcb1 was an important and hub gene and node in the hypoxia preconditioning signal networks. The findings in the hub genes and integrated gene networks provide very useful information for further exploring the molecular mechanisms of hypoxia preconditioning.