Extracellular vesicles-transmitted long non-coding RNA MTUS2-5 promotes proliferation and vascularization of human vascular endothelial cells in patients with Budd-Chiari syndrome

Abstract

The high rates of misdiagnosis and untreated mortality with regard to Budd-Chiari syndrome (BCS) indicated the need to screen effective biomarkers. The aim of this study was to explore the function of extracellular vesicles (EVs) in patients with BCS as well as associated mechanisms. First, differentially expressed long non-coding RNAs (lncRNAs) from EVs separated from serum between BCS and healthy controls were screened using microarray analysis. Second, the proliferation, migration and tube formation of human vascular endothelial cells (HUVECs) were detected after EVs treatment, along with vascular endothelial growth factor (VEGF) levels and inflammatory factors from the cell supernatant. Last, the overexpressed lncRNA was transfected into the cells to further explore the mechanisms involved. Extracellular vesicles of BCS patients have significantly higher levels of lncRNA MTUS2-5 than healthy controls. Apparently, treatment with EVs from BCS or the ones transfected with plasmids that overexpress lncRNA MTUS2-5 enhances proliferation, migration and angiogenesis capacity. The results were considerably better than those obtained from treatment with EVs from healthy controls or transfection with the normal control plasmid, which also elevated the level of VEGF and inflammatory factors. Furthermore, FOS and PTGS2 were potentially regulated by the lncRNA MTUS2-5 transmitted by EVs. The lncRNA MTUS2-5 in EVs plays an important role in angiogenesis in the Budd-Chiari syndrome.

Keywords: Budd-Chiari syndrome; HUVECs; angiogenesis; extracellular vesicles; lncRNA MTUS2-5.