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Interleukin-1 beta-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells.


ABSTRACT: Id2 (inhibitor of DNA-binding 2), a member of the helix-loop-helix family of transcription regulators, plays important roles in cell proliferation and differentiation. Recent reports have documented that Id2 is up-regulated during vascular lesion formation and overexpression of Id2 promotes vascular smooth muscle cell (VSMC) proliferation. However, the transcriptional regulation of Id2 gene expression in VSMC remains unexplored.Using Northern- and Western-blot analyses, we documented that interleukin-1beta (IL-1beta) induced Id2 gene expression in VSMC in a time- and dose-dependent manner. Overexpression of early growth response-1 (Egr-1) in VSMC induced Id2 expression while IL-1beta-induced Id2 expression was abrogated in VSMC by the Egr-1 repressor, NGFI-A binding protein 2 (NAB2), expressed from an adenovirus. Overexpression of Egr-1 transactivated the Id2 promoter in reporter assays dependent on the presence of intact putative Egr-1 binding sites as determined by mutagenesis. Finally, electrophoretic mobility shift assays (EMSA) demonstrated that the Egr-1 protein can bind the Egr-1 sites derived from the human Id2 promoter in vitro and chromatin immunoprecipitation identified the putative Egr-1 site between -723 to -712 as the functional Egr-1 binding site in vivo.Our data demonstrate that IL-1beta-induced Id2 expression in VSMC is mediated by the transcription factor Egr-1 in VSMC.

SUBMITTER: Zhu X 

PROVIDER: S-EPMC2094110 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Interleukin-1 beta-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells.

Zhu Xiaojun X   Lin Yiming Y   Bacanamwo Methode M   Chang Lin L   Chai Rui R   Massud Ivana I   Zhang Jifeng J   Garcia-Barrio Minerva T MT   Thompson Winston E WE   Chen Yuqing E YE  

Cardiovascular research 20070622 1


<h4>Objective</h4>Id2 (inhibitor of DNA-binding 2), a member of the helix-loop-helix family of transcription regulators, plays important roles in cell proliferation and differentiation. Recent reports have documented that Id2 is up-regulated during vascular lesion formation and overexpression of Id2 promotes vascular smooth muscle cell (VSMC) proliferation. However, the transcriptional regulation of Id2 gene expression in VSMC remains unexplored.<h4>Methods and results</h4>Using Northern- and We  ...[more]

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