Abstract
The aim of this study is to screen the differentially expressed genes and genes with alternative splicing in PPIA overexpressing cells by transcriptome sequencing. Transcriptome sequencing was performed to identify differentially expressed genes and genes with altered alternative splicing in PPIA overexpressing cells and results were validated by real-time quantitative polymerase chain reaction. The biological function and pathways of those genes were further explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 157 significantly upregulated genes and 171 significantly downregulated genes were identified in PPIA overexpressing cells, and the splicing pattern of LHPP, APH1A, BRD1, and ORAI3 was found to be altered. GO analyses showed that the most enriched GO terms of the 157 upregulated genes included extracellular region, protein binding, and metal ion, and the most enriched GO terms of the 171 downregulated genes included binding neuron projection, protein binding, and endoplasmic reticulum unfolded protein response. Kyoto Encyclopedia of Genes and Genomes analyses showed that the 157 upregulated genes were mainly enriched in gastric acid secretion, Mitogen-activated protein kinase signaling pathway, etc, and the 171 downregulated genes were mainly enriched in transcriptional misregulation in cancer, Tumor necrosis factor signaling pathway, etc. The overexpression of PPIA in human umbilical vein endothelial cells causes changes in the expression of downstream genes and induces alternative splicing in multiple genes. PPIA alters the expression or the alternative splicing pattern of downstream genes, leading to pathogenesis of vascular endothelial injury by high glucose mediated through CyPA.