Construction of the network of critical paths on Blood-stasis syndrome of hypertension based on mRNA sequencing

Abstract

IntroductionThe objective of this study was to construct a critical network of pathways on Blood-stasis syndrome (BSS) relating to hypertension by using mRNA sequencing and database mining techniques. Methods52 cases of primary hypertension patients were collected and they were further classified into different types of Blood-stasis syndrome groups. Serum samples were collected from different groups and were used to culture Human umbilical vein endothelial cells (HUVECs) so as to establish the cell models of BSS. TRIzol reagent was used to extract total RNA of HUVECs and transcriptome sequencing and analysis was performed based on Solexa Genome Analyzer platform. The differentially expressed genes were compared between the different experimental groups using Office Excel software and the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analyze to the functional categories and enriched pathways of the differentially expressed genes. Interologous Interaction Database (I2D) was used to construct a protein-protein interaction (PPI) network of the genes in the common pathways of the different HTBS groups. The network was analyzed based on Betweenness centrality, then the hubs of the PPI network were identified as the key genes for Blood-stasis syndrome and linked together to build a critical network of pathways on Blood-stasis syndrome of hypertension. ResultsIn contrast with the normal control group (NC) group or the non-blood-stasis syndrome (HTNS) group, a total of 2 378 differentially expressed genes of different types of Blood-stasis syndrome of hypertension (HTBS) groups were selected out. With pathway or gene enrichment analysis using DAVID, 75 key genes in the common pathways with high levels of enrichment were obtained, and were imported into I2D to construct a PPI network. Based on the network analysis results, a critical network of pathways on Blood-stasis syndrome of hypertension were constructed, among which Ubiquitin C (UBC) was the bridge to link the key genes on Hypertension with Blood-stasis Syndrome. ConclusionDuring the process of hypertension, UBC, which plays a key role in maintaining cellular ubiquitin levels, could cause a series of pathological reactions and eventually lead to the occurrence of Blood-stasis syndrome.