Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells

Stelios Tsigkos, Zongmin Zhou, Anastasia Kotanidou, David Fulton, Spyros Zakynthinos, Charis Roussos, Andreas Papapetropoulos

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Angiopoietin-2 (Ang2) is a Tie-2 ligand that destabilizes vascular structures, allowing for neovascularization or vessel regression depending on local vascular endothelial cell growth factor (VEGF) concentrations. Although various stimuli have been shown to affect Ang2 expression, information on the underlying mechanisms involved in Ang2 production in endothelial cells (EC) is just beginning to emerge. In the present study, we have used adenovirus-mediated gene transfer and pharmacological inhibitors to examine the role of the PTEN/PI3-K/Akt pathway on Ang2 release. Inhibition of PI3-kinase with wortmannin led to a stimulation of basal Ang2 release in EC, while overexpression of an active form of Akt reduced Ang2. In addition, adenovirus-mediated gene transfer of the phosphatase PTEN stimulated Ang2 release. Incubation of the cells with Ang1, an agent that activates the PI3-K/Akt pathway in EC, reduced Ang2 release. This effect of Ang1 could be prevented by wortmannin and LY-294002 pretreatment. Similarly, in VEGF-treated EC the increase in Ang2 production observed was greater in the presence of a PI3-K inhibitor. Our observations that PTEN acts as a positive modulator of Ang2 release, while activation of the PI3-K/Akt pathway downregulates Ang2, reveal an additional mechanism through which the PTEN/PI3-K/Akt pathway could affect the angiogenic process.

Original languageEnglish (US)
Pages (from-to)506-511
Number of pages6
JournalJournal of Cellular Physiology
Volume207
Issue number2
DOIs
StatePublished - May 1 2006
Externally publishedYes

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Angiopoietin-2
Endothelial cells
Phosphatidylinositol 3-Kinases
Endothelial Cells
Lung
Gene transfer
Cell growth
Adenoviridae
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
PTEN Phosphohydrolase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Modulators
Genes
Blood Vessels
Down-Regulation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells. / Tsigkos, Stelios; Zhou, Zongmin; Kotanidou, Anastasia; Fulton, David; Zakynthinos, Spyros; Roussos, Charis; Papapetropoulos, Andreas.

In: Journal of Cellular Physiology, Vol. 207, No. 2, 01.05.2006, p. 506-511.

Research output: Contribution to journalArticle

Tsigkos S, Zhou Z, Kotanidou A, Fulton D, Zakynthinos S, Roussos C et al. Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells. Journal of Cellular Physiology. 2006 May 1;207(2):506-511. https://doi.org/10.1002/jcp.20592
Tsigkos, Stelios ; Zhou, Zongmin ; Kotanidou, Anastasia ; Fulton, David ; Zakynthinos, Spyros ; Roussos, Charis ; Papapetropoulos, Andreas. / Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells. In: Journal of Cellular Physiology. 2006 ; Vol. 207, No. 2. pp. 506-511.
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