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

Autor: Yuqing E. Chen, Ivana Massud, Rui Chai, Winston E. Thompson, Xiaojun Zhu, Lin Chang, Methode Bacanamwo, Minerva Garcia-Barrio, Yiming Lin, Jifeng Zhang
Rok vydání: 2007
Předmět:
Transcriptional Activation
Chromatin Immunoprecipitation
Physiology
Interleukin-1beta
Myocytes
Smooth Muscle

Gene Expression
Repressor
Electrophoretic Mobility Shift Assay
Biology
Article
Muscle
Smooth
Vascular

Adenoviridae
Physiology (medical)
Gene expression
Transcriptional regulation
Humans
Electrophoretic mobility shift assay
RNA
Messenger

Promoter Regions
Genetic

Transcription factor
Cells
Cultured

Early Growth Response Protein 1
Inhibitor of Differentiation Protein 2
Regulation of gene expression
Analysis of Variance
Binding Sites
Dose-Response Relationship
Drug

Binding protein
Molecular biology
Stimulation
Chemical

Repressor Proteins
body regions
Gene Expression Regulation
Mutagenesis
Site-Directed

Cardiology and Cardiovascular Medicine
Chromatin immunoprecipitation
hormones
hormone substitutes
and hormone antagonists
Zdroj: Cardiovascular Research. 76:141-148
ISSN: 0008-6363
DOI: 10.1016/j.cardiores.2007.06.015
Popis: 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 and results Using Northern- and Western-blot analyses, we documented that interleukin-1β (IL-1β) 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-1β-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-1β-induced Id2 expression in VSMC is mediated by the transcription factor Egr-1 in VSMC.
Databáze: OpenAIRE