The effect of hypoxia on gene expression and signaling pathway in 3D cultured cerebral cortex cells / 中国医师杂志

ABSTRACT

Objective@#To explore potential therapeutic targets for neonatal hypoxic brain injury, we analyzed the effects of hypoxia on the gene expression profiles and signaling pathway in 3D cultured cerebral cortex cells.@*Methods@#R studio software was used to analyze the differentially expressed genes of hypoxia treated cerebral cortex cell data (GSE112137) which was downloaded from GEO database. Gene Oncology and KEGG software were used to enrich the molecular function, biological process and signaling pathways of differentially expressed genes. Then String and Cytoscape software were adapted to analyzed gene interaction network between these genes.@*Results@#There were 395 increasing genes and 185 decreasing genes (Change Fold≥2) were identified in hypoxic cerebral cells compared with the control groups. Most elevated genes were mainly related with molecular function including dioxygenase activity, isomerase activity and misfolded protein binding, while the decreasing genes were enriched in RNA polymerase Ⅱ proximal promoter sequence-specific DNA binding. Biological process enrichment analysis revealed that hypoxia up-regulated genes were associated with endoplasmic reticulum stress, oxidation-reduction process and glycolysis, while down-regulated genes were involved in the progress of neural development and cell differentiation. KEGG pathway enrichment results indicated hypoxia increasing genes were mainly related with endoplasmic reticulum protein processing, glycolysis, amino acid biosynthesis, and decreasing genes were mainly enriched in Parkinson′s disease signaling pathway.@*Conclusions@#Hypoxia in human cerebral cortex cells could cause endoplasmic reticulum stress, protein misfolding and metabolic abnormalities, inhibited the development of neuron cells. Drugs targeting these process may be beneficial to alleviate cerebral hypoxia injury.