Runx1 promotes angiogenesis by downregulation of insulin-like growth factor-binding protein-3

Ken Iwatsuki, Kiyoko Tanaka, Tsuyoshi Kaneko, Ritsuko Kazama, Shiki Okamoto, Yuki Nakayama, Yoshiaki Ito, Masanobu Satake, Shin Ichiro Takahashi, Atsushi Miyajima, Toshio Watanabe, Takahiko Hara

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Mouse embryos lacking the Runx1 transcription factor exhibit an angiogenic defect accompanied by the absence of hematopoietic stem cells (HSCs). To ask whether Runx1 plays a direct role in angiogenesis, we established a novel endothelial progenitor cell line, designated AEL-ΔR1, from the aorta-gonad-mesonephros (AGM) region of Runx1-null mouse. We introduced Runx1 cDNA into AEL-ΔR1 cells under the doxycycline-inducible promoter. The ability of AEL-ΔR1 cells to form vascular networks on matrigel was highly enhanced by the restored expression of Runx1. By molecular comparison of mRNAs in AEL-ΔR1 cells before and after the induction of Runx1, we found that mRNA expression of insulin-like growth factor-binding protein 3 (IGFBP-3) is down-regulated by Runx1. Gel retardation and reporter assays revealed that Runx1 binds to the promoter region of mouse IGFBP-3 gene and represses its transcription. When IGFBP-3 was exogenously added in the matrigel assay, the angiogenesis-enhancing activity of Ruox1 was suppressed in a dose-dependent manner. These results demonstrate that Runx1 is directly involved in angiogenesis by repression of IGFBP-3 mRNA expression.

Original languageEnglish
Pages (from-to)1129-1137
Number of pages9
JournalOncogene
Volume24
Issue number7
DOIs
Publication statusPublished - 2005 Feb 10

Keywords

  • Angiogenesis
  • Endothelial cell
  • IGFBP-3
  • Runx1
  • Transcriptional repression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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