Celastrol protects TGF b1 induced endothelial mesenchymal transition
The endothelial to mesenchymal transition (EndMT) in endothelial cells contributes to the development of cardiac fibrosis, ultimately leading to cardiac remodeling. In this study, the effects and molecular mechanisms of celastrol (CEL) on transforming growth factor b1 (TGF b1) induced EndMT in human umbilical vein endothelial (HUVEC 12) cells were investigated. The presented data demonstrated that CEL significantly blocked the morphology change of HUVEC 12 cells induced by TGF b1 without cell cytotoxicity. In accordance with these findings, CEL blocked TGF b1 induced EndMT as evidenced by the inhibition of the mesenchymal markers, including collagen I, III, a SMA, fibronectin mRNA expression, and the increase in the mRNA expression of endothelial cell marker CD31. These changes were also confirmed by double immunofluorescence staining of CD31 and vimentin. The in vitro scratch assay showed that CEL inhibited the migration capacity of the transitioned endothelial cells induced by TGF b1. Further experiments showed that the beneficial effect of CEL on blocking the EndMT in HUVEC 12 cells was associated with the suppression of the TGF b1/Smads signalling pathway, which was also confirmed by the inhibition of its downstream transcription factor snail1, twist1, twist2, ZEB1 and ZEB2. These results indicate that CEL blocks TGF b1 induced EndMT through TGF b1/Smads signalling pathway and suggest that it may be a feasible therapy for cardiac fibrosis diseases.
Journal of Huazhong University of Science and Technology [Medical Sciences]