Hypoxia-specific upregulation of the endogenous human VEGF-A gene by hypoxia-driven expression of artificial transcription factor

Tomoaki Mori, Jun Sasaki, Takuya Kanamori, Yasuhiro Aoyama, Takashi Sera

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Activation of vascular endothelial growth factor A (VEGF-A) is an attractive approach to treatment of ischemic diseases. Although zinc-finger-based artificial transcription factors (ATFs) were constructed for human VEGF-A and constitutive expression of ATFs upregulated the endogenous VEGF-A gene expression, activation of VEGF-A specifically in ischemic tissues is desirable for therapeutic application of ATF technology. Here, we describe hypoxia-specific activation of human VEGF-A gene by hypoxia-driven expression of the ATF. We constructed a hypoxia-driven promoter for the ATF expression and placed it upstream of the ATF-encoding regions. The resulting hypoxia-driven expression plasmid induced the ATF expression in hypoxia but not in normoxia, and the hypoxia-specific expression of the ATF activated the VEGF-A expression specifically in hypoxia. Thus, the engineered expression system of ATFs may enable activation of VEGF-A expression specifically in ischemic tissues without affecting normal, healthy tissues in vivo.

Original languageEnglish
Pages (from-to)845-848
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume390
Issue number3
DOIs
Publication statusPublished - Dec 18 2009
Externally publishedYes

Keywords

  • Artificial transcription factor
  • Hypoxia
  • Hypoxia-response element
  • Ischemic diseases
  • Vascular endothelial growth factor A
  • Zinc-finger protein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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