title: Celastrol protects TGF-β1-induced endothelial-mesenchymal transition.
abstract: 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-β1 (TGF-β1)-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-β1 without cell cytotoxicity. In accordance with these findings, CEL blocked TGF-β1-induced EndMT as evidenced by the inhibition of the mesenchymal markers, including collagen I, III, α-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-β1. 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-β1/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-β1-induced EndMT through TGF-β1/Smads signalling pathway and suggest that it may be a feasible therapy for cardiac fibrosis diseases.
authors.affiliation: Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China. ganxuedong123@126.com.
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Gan
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053978:Pentacyclic Triterpenes; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D005819:Genetic Markers; D053978:Pentacyclic Triterpenes; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; C050414:celastrol
keywords: TGF-β1/Smads signaling pathway; cardiac fibrosis; celastrol; endothelial-mesenchymal transition; endothelium