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 |
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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 |
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