VEGF selectively induces Down syndrome critical region 1 gene expression in endothelial cells: A mechanism for feedback regulation of angiogenesis?

Yong Gang Yao, Elia J. Duh

Research output: Contribution to journalArticlepeer-review

Abstract

The Down syndrome critical region 1 (DSCR1) gene (also known as MCIP1, Adapt78) encodes a regulatory protein that binds to calcineurin catalytic A subunit and acts as a regulator of the calcineurin-mediated signaling pathway. We show in this study that DSCR1 is greatly induced in endothelial cells in response to VEGF, TNF-α, and A23187 treatment, and that this up-regulation is inhibited by inhibitors of the calcineurin-NFAT (nuclear factor of activated T cells) signaling pathway as well as by PKC inhibition and a Ca 2+ chelator. We hypothesized that the up-regulation of DSCR1 gene expression in endothelial cells could act as an endogenous feedback inhibitor for angiogenesis by regulating the calcineurin-NFAT signaling pathway. Our transient transfection analyses confirm that the overexpression of DSCR1 abrogates the up-regulation of reporter gene expression driven by both the cyclooxygenase 2 and DSCR1 promoters in response to stimulators. Our results indicate that DSCR1 up-regulation may represent a potential molecular mechanism underlying the regulation of angiogenic genes activated by the calcineurin-NFAT signaling pathway in endothelial cells.

Original languageEnglish (US)
Pages (from-to)648-656
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume321
Issue number3
DOIs
StatePublished - Aug 27 2004

Keywords

  • Calcineurin-NFAT
  • Cox-2
  • DSCR1
  • Endothelial cell
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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