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Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis

The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been prev...

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Autores principales: Zins, Karin, Pomyje, Jiri, Hofer, Erhard, Abraham, Dietmar, Lucas, Trevor, Aharinejad, Seyedhossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907885/
https://www.ncbi.nlm.nih.gov/pubmed/24451137
http://dx.doi.org/10.3390/ijms15011538
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author Zins, Karin
Pomyje, Jiri
Hofer, Erhard
Abraham, Dietmar
Lucas, Trevor
Aharinejad, Seyedhossein
author_facet Zins, Karin
Pomyje, Jiri
Hofer, Erhard
Abraham, Dietmar
Lucas, Trevor
Aharinejad, Seyedhossein
author_sort Zins, Karin
collection PubMed
description The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been previously linked to multiple aspects of cardiovascular injury. In this study, we showed constitutive expression of Egr-1 in cultured human ventricular cardiac fibroblasts, used adenoviral mediated gene transfer to study the effects of continuous Egr-1 overexpression and studied downstream transcription by Western blotting, immunohistochemistry and siRNA transfection. Apoptosis was assessed by fluorescence microscopy and flow cytometry in the presence of caspase inhibitors. Overexpression of Egr-1 directly induced apoptosis associated with caspase activation in human cardiac fibroblast cultures in vitro assessed by fluorescence microscopy and flow cytometry. Apoptotic induction was associated with a caspase activation associated loss of mitochondrial membrane potential and transient downstream transcriptional up-regulation of the pro-apoptotic gene product Siva-1. Suppression of Siva-1 induction by siRNA partially reversed Egr-1 mediated loss of cell viability. These findings suggest a previously unknown role for Egr-1 and transcriptional regulation of Siva-1 in the control of cardiac accessory cell death.
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spelling pubmed-39078852014-01-31 Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis Zins, Karin Pomyje, Jiri Hofer, Erhard Abraham, Dietmar Lucas, Trevor Aharinejad, Seyedhossein Int J Mol Sci Article The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been previously linked to multiple aspects of cardiovascular injury. In this study, we showed constitutive expression of Egr-1 in cultured human ventricular cardiac fibroblasts, used adenoviral mediated gene transfer to study the effects of continuous Egr-1 overexpression and studied downstream transcription by Western blotting, immunohistochemistry and siRNA transfection. Apoptosis was assessed by fluorescence microscopy and flow cytometry in the presence of caspase inhibitors. Overexpression of Egr-1 directly induced apoptosis associated with caspase activation in human cardiac fibroblast cultures in vitro assessed by fluorescence microscopy and flow cytometry. Apoptotic induction was associated with a caspase activation associated loss of mitochondrial membrane potential and transient downstream transcriptional up-regulation of the pro-apoptotic gene product Siva-1. Suppression of Siva-1 induction by siRNA partially reversed Egr-1 mediated loss of cell viability. These findings suggest a previously unknown role for Egr-1 and transcriptional regulation of Siva-1 in the control of cardiac accessory cell death. Molecular Diversity Preservation International (MDPI) 2014-01-21 /pmc/articles/PMC3907885/ /pubmed/24451137 http://dx.doi.org/10.3390/ijms15011538 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zins, Karin
Pomyje, Jiri
Hofer, Erhard
Abraham, Dietmar
Lucas, Trevor
Aharinejad, Seyedhossein
Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
title Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
title_full Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
title_fullStr Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
title_full_unstemmed Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
title_short Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
title_sort egr-1 upregulates siva-1 expression and induces cardiac fibroblast apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907885/
https://www.ncbi.nlm.nih.gov/pubmed/24451137
http://dx.doi.org/10.3390/ijms15011538
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