title: High glucose induced endothelial to mesenchymal transition in human umbilical vein endothelial cell.
abstract: Studies have shown that endothelial-to-mesenchymal transition (EndMT) could contribute to the progression of diabetic nephropathy, diabetic renal fibrosis, and cardiac fibrosis. The aim of this study was to investigate the influence of high glucose and related mechanism of MAPK inhibitor or specific antioxidant on the EndMT.
  
  
  
  In vitro human umbilical vein endothelial cells (HUVEC) were cultured with 11mM, 30mM, 60mM and 120mM glucose for 0, 24, 48, 72 and 168h. Endothelial cell morphology was observed with microscope, and RT-PCR was used to detect mRNA expression of endothelial markers VE-cadherin and CD31, mesenchymal markers α-SMA and collagen I, and transforming growth factor TGF-β1. Immunofluorescence staining was performed to detect the expression of CD31 and α-SMA. The concentration of TGF-β1 in the supernatant was detected by ELISA. ERK1/2 phosphorylation level was detected by Western blot analysis.
  
  
  
  High glucose induced EndMT and increased the TGF-β1 level in HUVEC cells. Cells in high glucose for 7 days showed a significant decrease in mRNA expression of CD31 and VE-cadherin, and a significant increase in that of α-SMA and collagen I, while lost CD31 staining and acquired α-SMA staining. ERK signaling pathway blocker PD98059 significantly attenuated the high glucose-induced increase in the ERK1/2 phosphorylation level. PD98059 and NAC both inhibited high glucose-induced TGF-β1 expression and attenuated EndMT marker protein synthesis.
  
  
  
  High glucose could induce HUVEC cells to undergo EndMT. NAC and ERK signaling pathway may play important role in the regulation of the TGF-β1 biosynthesis during high glucose-induced EndMT.
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China; Department of Cardiology, Beijing Anzhen Hospital, Beijing, China.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Yu
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.lastname: Suriguga
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gong
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Ning-Xuan
authors.initials: NX
authors.lastname: Cui
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Beijing, China; Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing, China. Electronic address: duxinheart@sina.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.affiliation: School of Biological Science and Medical Engineering, Beihang University, Beijing, China. Electronic address: yizc@buaa.edu.cn.
authors.forename: Zong-Chun
authors.initials: ZC
authors.lastname: Yi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D000111:Acetylcysteine; D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D005419:Flavonoids; D005947:Glucose; D048052:Mitogen-Activated Protein Kinase 3; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000099152:Cadherin 5; C541116:ACTA2 protein, human; C508960:TGFB1 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Endothelial to mesenchymal transition; High glucose; NAC; PD98059; TGF-β1