The effect and underlying mechanism of miRNA-506 regulating TGF-β1-induced endothelial-mesenchymal transition of human aortic endothelial cell lysates

Abstract

Objective To investigate the effect and the underlying mechanism of miRNA(miR)-506 regulating transforming growth factor-β1 (TGF-β1)-induced endothelial-mesenchymal transition of human aortic endothelial cell lysates. Methods In this study, miR-506 and inhibitory members of the ASPP family (iASPP) were selected as the study objects. First, the expression of miR-506 in human aortic endothelial cell lysates (HAEC) lysate was detected under different concentrations of TGF-β1. The expression of platelet endothelial cell adhesion molecule-1 (CD31), endothelium-cadherin (VE-cadherin), fibroblast-specific protein-1 (FSP1), α-smooth muscle actin (α-SMA) and N-cadherin was determined after miR-506 mimics/mimic negative control (NC) transfection into HAEC treated with or without TGF-β1. Then the expression levels of iASPP in miRNA-506 mimics/mimic NC-transfected HAECs treated with or without TGF-β1 were determined. Finally, the protein expression of CD31, VE-cadherin, FSP1 and α-SMA in HAEC transfected with miR-506 mimics/mimic NC was determined after iASPP overexpression. Results TGF-β1 can induce human aortic endothelial cell mesenchymal transition, down-regulate CD31 and VE-cadherin expression while up-regulate FSP1, α-SMA and N-cadherin expression; TGF-β1 inhibited miR-506 expression, promoted iASPP expression; miR-506 transfection into HAECs up-regulated CD31 and VE-cadherin e-xpression while up-regulate FSP1, α-SMA and N-cadherin expression; miR-506 could downregulate the expression of iASPP; the overexpression of iASPP increased the expression of FSP1, α-SMA and N-cadherin, down-regulated CD31 and VE-cadherin and promoted the transformation of human aortic endothelial cells. Conclusions The transfection of iASPP plasmid promoted the endothelial-mesenchymal transition of human aortic endothelial cell lysates. The transfection of miR-506 inhibited the expression of iASPP and inhibited the endothelial-mesenchymal transition of human aortic endothelial cell lysates induced by TGF-β1. Key words: MicroRNAs; Intracellular signaling peptides and proteins; Tumor suppressor protein p53; Transforming growth factor beta1; Aorta; Endothelial cells; Biotransformation