alexa Regulation of VEGF-A Expression in Endothelial Cells by Transcriptional Gene Activation or Transcriptional Gene Silencing: Analysis of Genome Wide Transcriptional Response | Abstract
ISSN: 2329-6682

Gene Technology
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Research Article

Regulation of VEGF-A Expression in Endothelial Cells by Transcriptional Gene Activation or Transcriptional Gene Silencing: Analysis of Genome Wide Transcriptional Response

Tiia Husso1, Mikko P. Turunen1 and Seppo Yla-Herttuala1,2*
1Department of Biotechnology and Molecular Medicine, A.I.Virtanen Institute, University of Eastern Finland, Finland
2Science Service Center and Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland
Corresponding Author : Seppo Yla-Herttuala
A.I.Virtanen Institute for Molecular Sciences
University of Eastern Finland
P.O. Box 1627, FIN-70211
Kuopio, Finland
Tel: 0020 2 2683147
E-mail: [email protected]
Received May 13, 2015; Accepted June 01, 2015; Published June 03, 2015
Citation: Husso T, Turunen MP, Yla-Herttuala S (2015) Regulation of VEGF-A Expression in Endothelial Cells by Transcriptional Gene Activation or Transcriptional Gene Silencing: Analysis of Genome Wide Transcriptional Response. Gene Technol 4:122. doi: 10.4172/2329-6682.1000122
Copyright: © 2015 Husso T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Vascular endothelial growth factor (VEGF-A) is an important gene in many diseases, such as cancer and cardiovascular diseases. We investigated changes in genome-wide gene expression patterns in murine endothelial cells when the expression of VEGF-A was epigenetically modulated using promoter targeted small hairpin RNAs (shRNAs). Murine endothelial cells were transduced with lentiviral vectors expressing shRNAs that are complementary to the gene promoter. Gene expression array experiments were conducted to investigate genome-wide mRNA expression changes caused by up- and downregulating VEGF-A. There were several hundreds of differentially expressed genes according to the applied statistical criteria. We noticed that the effects of downregulating VEGF-A were much more wide-spread than the effects of VEGF-A upregulation. Our in silico analysis revealed that a number of different biological processes are altered due to epigenetic effects on VEGF-A expression. One of the main regulators of VEGF-A mediated transcriptional response was found to be transcription factor ATF-4. This is the first study showing the transcriptional response to epigenetic modification of VEGF-A expression in endothelial cells. Epigenetic gene regulation represents a natural gene regulatory mechanism and these results reveal previously unknown implications of VEGF-A regulation in endothelial cells.

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