Identification and Verification of Candidate Genes Regulating Human Umbilical Vein Endothelial Cells Behavior Under Hyperglycemia

Abstract

Background: Diabetes is a metabolic disease that has been widely demonstrated to be correlated with many microvascular and macrovascular diseases that seriously damage the patient’s life quality. This study intended to investigate the underlying molecular mechanisms of endothelial dysfunction under hyperglycemia. Methods: The gene expression profile of GSE49524 was downloaded and differentially expressed genes (DEGs) in hyperglycemia human umbilical cord endothelial cells (HUVECs) samples compared with normoglycemia HUVECs samples were identified by R software. Afterward, we analyzed the data by applying a combination of the bioinformatics method and used the microRNAs (miRNAs) databases to predict microRNAs that target key genes. The expression of the top 10 differentially expressed genes was validated through quantitative real-time PCR (qRT-PCR). Results: A total of 65 genes were distinguished as DEGs. The dominant GO (gene ontology) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways which were significantly overrepresented in the hyperglycemia HUVECs were identified. The results of the protein-protein interaction networks demonstrated that fibronectin 1 (FN1) is of the highest degree. In addition, several predicted miRNAs that target FN1 were obtained too. The further verification of the top 10 DEGs through qRT-PCR illustrated that nine of the up-regulated DEGs were up-regulated significantly in the hyperglycemia group when compared to the control group. Conclusions:This exploratory study may help to prompt an understanding of the underlying molecular mechanisms of the effect of hyperglycemia on the behavior of HUVECs and contribute to the production of effective therapeutic interventions.