Protective Effect of Spironolactone on Endothelial-to-Mesenchymal Transition in HUVECs via Notch Pathway

Abstract

Background: Fibrosis results in excessive buildup of extracellular matrix proteins along with abnormalities in structure and is partly derived by a process involving transforming growth factor β (TGF-β) called endothelial-to-mesenchymal transition (EndMT). We investigated whether the aldosterone receptor-blocker spironolactone could abrogate TGF-β-induced fibrosis in EndMT and the underlying mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) were divided into 5 groups for treatment: blank; vehicle control; TGF-β (10 ng/ml); spironolactone (1 μM)+TGF-β; and spironolactone+TGF-β+DAPT (10 μM). Cell chemotaxis was assayed by transwell assay. The expression of CD31 and vimentin was determined by Immunofluorescence staining and western blot analysis. Notch1 protein level was detected by western blot analysis. Results: Spironolactone significantly prevented TGF-β-stimulated EndMT by down-regulate vimentin and up-regulate CD31 in HUVECs (pConclusion: Spironolactone may have a protective role in TGF-β-induced EndMT in HUVECs mediated by the Notch signal pathway.

Keywords

• Spironolactone
• Fibrosis
• EndMT
• TGF-β
• Notch pathway
• HUVEC