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Early growth response factor-1 is a critical transcriptional mediator of peroxisome proliferator-activated receptor-gamma 1 gene expression in human aortic smooth muscle cells
Fu, MG; Zhang, JF; Lin, YM; Zhu, XJ; Ehrengruber, MU; Chen, YQE
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2002-07-26
DOI10.1074/jbc.M203748200
277期:30页:26808-26814
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]NF-KAPPA-B ; ENDOTHELIAL-CELLS ; BINDING-PROTEINS ; GAMMA-2 PROMOTER ; PPAR-GAMMA ; EGR-1 ; ELEMENT ; PPAR-GAMMA-2 ; ORGANIZATION ; MODULATION
英文摘要

To explore the molecular mechanisms of PPARgamma1 gene expression in vascular smooth muscle cells (VSMC), we hypothesized that early growth-response factor-1 (Egr-1) might be a transcriptional mediator of the growth factor- and cytokine-induced PPARgamma1 gene expression since a putative Egr-1 binding element was found in the human PPARgamma1 promoter. In this study, we document that overexpression of Egr-1 activates the human PPARgamma1 promoter in both VSMC and HepG2 cells. Using Northern blot analysis, we observed that growth factors and cytokines such as PDGF, bFGF, Ang 11, TNFalpha, and IL-1beta induce Egr-1 expression prior to PPARgamma1 up-regulation in human VSMC. In addition, overexpression of a constitutively active form of Egr-1 by adenoviral gene transfer in VSMC dramatically induced PPARgamma1 gene expression by 6-8-fold, and overexpression of NAB2, a potent negative feedback regulator of Egr-1, abrogated the growth factor- and cytokine-induced PPARgamma1 expression in VSMC. Furthermore, we demonstrate with gel mobility shift and transient transfection assays that the putative Egr-1 element in the human PPARgamma1 promoter specifically binds Egr-1 protein and becomes trans-activated by Egr-1. Taken together, our data demonstrate for the first time that Egr-1 is necessary and sufficient to activate human PPARgamma1 gene expression in VSMC.

语种英语
WOS记录号WOS:000177055900015
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被引频次:42[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/68057
专题基础医学院_心血管所
作者单位1.Univ Zurich, Brain Res Inst, CH-8057 Zurich, Switzerland
2.Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA
3.Peking Univ, Hlth Sci Ctr, Cardiovasc Res Inst, Beijing 100083, Peoples R China
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GB/T 7714
Fu, MG,Zhang, JF,Lin, YM,et al. Early growth response factor-1 is a critical transcriptional mediator of peroxisome proliferator-activated receptor-gamma 1 gene expression in human aortic smooth muscle cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2002,277(30):26808-26814.
APA Fu, MG,Zhang, JF,Lin, YM,Zhu, XJ,Ehrengruber, MU,&Chen, YQE.(2002).Early growth response factor-1 is a critical transcriptional mediator of peroxisome proliferator-activated receptor-gamma 1 gene expression in human aortic smooth muscle cells.JOURNAL OF BIOLOGICAL CHEMISTRY,277(30),26808-26814.
MLA Fu, MG,et al."Early growth response factor-1 is a critical transcriptional mediator of peroxisome proliferator-activated receptor-gamma 1 gene expression in human aortic smooth muscle cells".JOURNAL OF BIOLOGICAL CHEMISTRY 277.30(2002):26808-26814.
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