title: Advanced glycation end products induce endothelial-to-mesenchymal transition via downregulating Sirt 1 and upregulating TGF-β in human endothelial cells.
abstract: In the present study, we examined the advanced glycation end products- (AGEs-) induced endothelial-to-mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Results demonstrated that AGE-BSAs significantly reduced the cluster of differentiation 31 (CD 31) expression, whereas they promoted the expression of fibroblast-specific protein-1 (FSP-1), α-smooth muscle antibody (α-SMA), and collagen I at both mRNA and protein levels in HUVECs. And the AGE-BSAs also promoted the receptors for AGEs (RAGEs) and receptor I for TGF-β (TGFR I) markedly with a dose dependence, whereas the Sirt 1 was significantly downregulated by the AGE-BSA at both mRNA and protein levels. Moreover, the Sirt 1 activity manipulation with its activator, resveratrol (RSV), or its inhibitor, EX527, markedly inhibited or ameliorated the AGE-mediated TGF-β upregulation. And the manipulated Sirt 1 activity positively regulated the AGE-induced CD31, whereas it negatively regulated the AGE-induced FSP-1. Thus, Sirt 1 was confirmed to regulate the AGE-induced EndMT via TGF-β. In summary, we found that AGE-BSA induced EndMT in HUVECs via upregulating TGF-β and downregulating Sirt 1, which also negatively regulated TGF-β in the cell. This study implied the EndMT probably as an important mechanism of AGE-induced cardiovascular injury.
authors.affiliation: Pacing Electrophysiology Division, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang 830054, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Pacing Electrophysiology Division, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang 830054, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Pacing Electrophysiology Division, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang 830054, China.
authors.forename: Tian-yi
authors.initials: TY
authors.lastname: Gan
authors.affiliation: Pacing Electrophysiology Division, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang 830054, China.
authors.forename: Guo-jun
authors.initials: GJ
authors.lastname: Xu
authors.affiliation: Pacing Electrophysiology Division, First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang 830054, China.
authors.forename: Bao-peng
authors.initials: BP
authors.lastname: Tang
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D056564:Sirtuin 1 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D017127:Glycation End Products, Advanced; D016212:Transforming Growth Factor beta; C447939:SIRT1 protein, human; D056564:Sirtuin 1