Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs

Jeong Heon Lee, Taehoon Chun, Sang Yoon Park, Seung Bae Rho

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Interferon regulatory factor-1 (IRF-1) is a tumor suppressor and transcriptional modulator that can regulate gene expression involved in cell growth control, induction of apoptosis, and post-translation modification. In this study, we found that IRF-1 inhibits endothelial cell angiogenesis using human umbilical vein endothelial cell (HUVECs) culture system. In addition, IRF-1 directly inhibited the tube formation of endothelial cells on Matrigel and reduced the expression of p-Akt, and p-eNOS, which play a significant role in angiogenesis when stimulated by VEGF. We also demonstrate that C-terminal region including transactivation domain (TA) of IRF-1 functions as a signal for its angiostatic activity, and is spliced in human tumor tissues. These findings indicate that splicing variant involving exons 7 of IRF-1 could potentially modulate anti-angiogenic effect of IRF-1. In overall, this study provides the first evidence for anti-angiogenic role of IRF-1, which may have therapeutic values for cancer and angiogenesis-associated diseases.

Original languageEnglish
Pages (from-to)1654-1662
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number9
DOIs
Publication statusPublished - 2008 Sep 1

Keywords

  • Alternative splicing
  • Angiogenesis
  • CAM
  • Endothelial cell
  • Interferon regulatory factor
  • Vessel sprouting

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics
  • Medicine(all)

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