NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells

Markus Lucerna, Diana Mechtcheriakova, Alexandra Kadl, Gernot Schabbauer, Romana Schäfer, Florian Gruber, Yuri Koshelnick, Horst Dietmar Müller, Katja Issbrücker, Matthias Clauss, Bernd R. Binder, Erhard Hofer

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

In this study we have investigated the role of a specific corepressor of EGR-1, NAB2, to down-regulate vascular endothelial growth factor (VEGF)-induced gene expression in endothelial cells and to inhibit angiogenesis. Firstly, we show a reciprocal regulation of EGR-1 and NAB2 following VEGF treatment. During the initial phase EGR-1 is rapidly induced and NAB2 levels are down-regulated. This is followed by a reduction of EGR-1 and a concomitant increase of NAB2. Secondly, using the tissue factor gene as a readout for VEGF-induced and EGR-1-regulated gene expression we demonstrate that NAB2 can completely block VEGF-induced tissue factor reporter gene activity. Thirdly, by adenovirus-mediated expression we show that NAB2 inhibits up-regulation of tissue factor, VEGF receptor-1, and urokinase plasminogen activator mRNAs even when a combination of VEGF and bFGF is used for induction. In addition, NAB2 overexpression significantly reduced tubule and sprout formation in two different in vitro angiogenesis assays and largely prevented the invasion of cells and formation of vessel-like structures in the murine Matrigel model. These data suggest that NAB2 regulation represents a mechanism to guarantee transient EGR-1 activity following exposure of endothelial cells to VEGF and that NAB2 overexpression could be used to inhibit signals involved in the early phase of angiogenesis.

Original languageEnglish (US)
Pages (from-to)11433-11440
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number13
DOIs
StatePublished - Mar 28 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lucerna, M., Mechtcheriakova, D., Kadl, A., Schabbauer, G., Schäfer, R., Gruber, F., Koshelnick, Y., Müller, H. D., Issbrücker, K., Clauss, M., Binder, B. R., & Hofer, E. (2003). NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells. Journal of Biological Chemistry, 278(13), 11433-11440. https://doi.org/10.1074/jbc.M204937200