Interleukin-1 beta-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells.
Cardiovasc Res
; 76(1): 141-8, 2007 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-17631285
ABSTRACT
OBJECTIVE:
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. METHODS ANDRESULTS:
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.CONCLUSIONS:
Our data demonstrate that IL-1beta-induced Id2 expression in VSMC is mediated by the transcription factor Egr-1 in VSMC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Miócitos de Músculo Liso
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Proteína 1 de Resposta de Crescimento Precoce
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Proteína 2 Inibidora de Diferenciação
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Interleucina-1beta
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2007
Tipo de documento:
Article