The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial Cells
Vascular endothelial growth factor (VEGF) is important for maintaining healthy endothelium, which is crucial for vascular integrity. In this paper, we show that VEGF stimulates the nuclear translocation of endothelial differentiation-related factor 1 (EDF1), a highly conserved intracellular protein...
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doaj-5fe60134985a4d4188125ae8b6b96e7e2020-11-24T22:59:56ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-06-01197183010.3390/ijms19071830ijms19071830The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial CellsAlessandra Cazzaniga0Laura Locatelli1Sara Castiglioni2Jeanette Maier3Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università degli Studi di Milano, I-20157 Milan, ItalyDipartimento di Scienze Biomediche e Cliniche L. Sacco, Università degli Studi di Milano, I-20157 Milan, ItalyDipartimento di Scienze Biomediche e Cliniche L. Sacco, Università degli Studi di Milano, I-20157 Milan, ItalyDipartimento di Scienze Biomediche e Cliniche L. Sacco, Università degli Studi di Milano, I-20157 Milan, ItalyVascular endothelial growth factor (VEGF) is important for maintaining healthy endothelium, which is crucial for vascular integrity. In this paper, we show that VEGF stimulates the nuclear translocation of endothelial differentiation-related factor 1 (EDF1), a highly conserved intracellular protein implicated in molecular events that are pivotal to endothelial function. In the nucleus, EDF1 serves as a transcriptional coactivator of peroxisome proliferator-activated receptor gamma (PPARγ), which has a protective role in the vasculature. Indeed, silencing EDF1 prevents VEGF induction of PPARγ activity as detected by gene reporter assay. Accordingly, silencing EDF1 markedly inhibits the stimulatory effect of VEGF on the expression of FABP4, a PPARγ-inducible gene. As nitric oxide is a marker of endothelial function, it is noteworthy that we report a link between EDF1 silencing, decreased levels of FABP4, and nitric oxide production. We conclude that EDF1 is required for VEGF-induced activation of the transcriptional activity of PPARγ.http://www.mdpi.com/1422-0067/19/7/1830endothelial cellsvascular endothelial growth factorPeroxisome proliferator-activated receptor γEndothelial Differentiation-related factor 1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alessandra Cazzaniga Laura Locatelli Sara Castiglioni Jeanette Maier |
spellingShingle |
Alessandra Cazzaniga Laura Locatelli Sara Castiglioni Jeanette Maier The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial Cells International Journal of Molecular Sciences endothelial cells vascular endothelial growth factor Peroxisome proliferator-activated receptor γ Endothelial Differentiation-related factor 1 |
author_facet |
Alessandra Cazzaniga Laura Locatelli Sara Castiglioni Jeanette Maier |
author_sort |
Alessandra Cazzaniga |
title |
The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial Cells |
title_short |
The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial Cells |
title_full |
The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial Cells |
title_fullStr |
The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial Cells |
title_full_unstemmed |
The Contribution of EDF1 to PPARγ Transcriptional Activation in VEGF-Treated Human Endothelial Cells |
title_sort |
contribution of edf1 to pparγ transcriptional activation in vegf-treated human endothelial cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-06-01 |
description |
Vascular endothelial growth factor (VEGF) is important for maintaining healthy endothelium, which is crucial for vascular integrity. In this paper, we show that VEGF stimulates the nuclear translocation of endothelial differentiation-related factor 1 (EDF1), a highly conserved intracellular protein implicated in molecular events that are pivotal to endothelial function. In the nucleus, EDF1 serves as a transcriptional coactivator of peroxisome proliferator-activated receptor gamma (PPARγ), which has a protective role in the vasculature. Indeed, silencing EDF1 prevents VEGF induction of PPARγ activity as detected by gene reporter assay. Accordingly, silencing EDF1 markedly inhibits the stimulatory effect of VEGF on the expression of FABP4, a PPARγ-inducible gene. As nitric oxide is a marker of endothelial function, it is noteworthy that we report a link between EDF1 silencing, decreased levels of FABP4, and nitric oxide production. We conclude that EDF1 is required for VEGF-induced activation of the transcriptional activity of PPARγ. |
topic |
endothelial cells vascular endothelial growth factor Peroxisome proliferator-activated receptor γ Endothelial Differentiation-related factor 1 |
url |
http://www.mdpi.com/1422-0067/19/7/1830 |
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