Tauroursodeoxycholic acid inhibits endothelial-mesenchymal transition in high glucose-treated human umbilical vein endothelial cells

Abstract

The high glucose-induced endothelial-mesenchymal transition (EndMT) may be the initial and underlying mechanism of diabetic vascular complications. Although tauroursodeoxycholic acid (TUDCA) plays various protective roles in diabetes and its complications, it’s unclear whether TUDCA inhibits the high glucose-induced EndMT. In this study, human umbilical vein endothelial cells (HUVECs) were treated with high glucose and intervened with TUDCA. The mRNA expression of fibroblast as well as endothelial markers, fibroblast specific protein 1 (FSP1), collagen I, CD31 and calcium adhesion protein 5, was detected. The protein content of FSP1 and CD31 was ascertained, with FSP1 distribution illustrated. The scratch assay was performed to evaluate the migratory ability of HUVECs. The protein content of TGF-β1 and Smad3, the distribution of Smad3 and the binding of Smad3 to the gene promoter of FSP1, were measured. The results firstly showed that TUDCA reversed the expression of EndMT-related genes in high glucose-treated HUVECs. Furthermore, TUDCA reduced FSP1 content with elevation in CD31, inhibited FSP1 distribution and attenuated morphological changes of high glucose-treated HUVECs. Meanwhile, TUDCA inhibited the high glucose-enhanced migratory ability of HUVECs. Mechanically, TUDCA prevented the binding of Smad3 to the gene promoter of FSP1 in high glucose-treated HUVECs, although it had little effect on the content of TGF-β1 and Smad3. In conclusion, TUDCA inhibited the high glucose-induced EndMT via preventing Smad3 from binding to the gene promoter of fibroblast markers, such as FSP1, in HUVECs.