title: TNF-α induces early growth response gene-1 expression via ERK1/2 activation in endothelial cells.
abstract: TNF-α and hyperglycemia are important factors contributing to vascular complications in obese and diabetic patients. The present studies aimed to examine, in endothelial cells, downstream signaling mechanisms that may ultimately link TNF-α and hyperglycemia to vascular pathology. Human umbilical vein endothelial cells were cultured and incubated with 10 ng/ml TNF-α and/or 25 mmol/l glucose. The expression of early growth response gene-1 (Egr-1) and ERK1/2 protein was quantified by Western blotting, and plasminogen activator inhibitor-1 (PAI-1) levels were measured by ELISA. Both glucose and TNF-α increased Egr-1 expression, while simultaneous exposure to the two factors exerted an additive effect. Furthermore, PAI-1 was also upregulated in the presence of TNF-α and glucose. The MEK inhibitor, PD98059, downregulated TNF-α-induced Egr-1 expression. TNF-α (10 ng/ml) increased ERK1/2 levels 1.76 ± 0.23-fold (P < 0.01) after 25 mmol/l glucose pretreatment, but added glucose did not enhance ERK1/2 activation when given subsequent to TNF-α treatment. TNF-α induced Egr-1 protein expression and PAI-1 levels through the ERK1/2 pathway. Differential regulation of Egr-1 expression by glucose and TNF-α in endothelial cells may be an important consideration in the mechanisms linking these factors to the development of vascular dysfunction in metabolic disorders such as diabetes.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of China Medical University, Heping District, Shenyang, Liaoning, China. vanilla421@163.com
authors.forename: Yanli
authors.initials: Y
authors.lastname: Cao
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.forename: Difei
authors.initials: D
authors.lastname: Wang
mesh_terms: D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017395:Plasminogen Activator Inhibitor 1; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3