Diabetologia

, Volume 44, Issue 6, pp 713–720

Transcription factor decoy for activator protein-1 (AP-1) inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor (PAI-1) gene expression in cultured human vascular smooth muscle cells

  • J. D. Ahn
  • R. Morishita
  • Y. Kaneda
  • K. U. Lee
  • J. Y. Park
  • Y. J. Jeon
  • H. S. Song
  • I. K. Lee
Article

DOI: 10.1007/s001250051680

Cite this article as:
Ahn, J., Morishita, R., Kaneda, Y. et al. Diabetologia (2001) 44: 713. doi:10.1007/s001250051680

Abstract

Aims/hypothesis. Multiple factors, including hyperglycaemia and angiotensin II (Ang II), stimulate plasminogen activator inhibitor-1 (PAI-1) gene expression in human vascular smooth muscle cells. This study tested the hypothesis that hyperglycaemia and Ang II stimulate PAI-1 gene expression through activator protein-1 (AP-1) binding sites. Methods. We evaluated the role of AP-1 in PAI-1 gene expression in human vascular smooth muscle cells under high d-glucose and Ang II stimulation using a double-stranded cis-element AP-1 oligodeoxynucleotide (decoy ODN). Results. Activator protein 1 activity was stimulated by high glucose and Ang II treatment and the AP-1 decoy ODN, but not a mismatched decoy ODN, competed for AP-1 activity. The increase in PAI-1 expression by high glucose and Ang II was significantly attenuated by the AP-1 decoy ODN (p < 0.05 or p < 0.01). The increase in PAI-1 expression by high glucose and Ang II action on AP-1 sites was also confirmed by promoter analysis of PAI-1. Activator protein 1 activation in response to either high glucose or co-stimulation with high glucose and Ang II was inhibited completely by calphostin C (a PKC inhibitor) and partially by genistein (a protein tyrosine kinase inhibitor). Conclusion/interpretation. This study shows that high glucose and Ang II stimulate PAI-1 expression through AP-1 binding sites. Signal transduction after AP-1 activation by both high glucose and Ang II largely depends on PKC activation. These data indicate an important role for AP-1 in PAI-1 expression. [Diabetologia (2001) 44: 713–720]

Keywords Decoy ODN glucose diabetes activator protein-1 (AP-1) plasminogen activator inhibitor-1. 
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© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • J. D. Ahn
    • 1
  • R. Morishita
    • 2
  • Y. Kaneda
    • 2
  • K. U. Lee
    • 3
  • J. Y. Park
    • 3
  • Y. J. Jeon
    • 4
  • H. S. Song
    • 4
  • I. K. Lee
    • 4
  1. 1.Institute for Medical Science, Keimyung University School of Medicine, Taegu, KoreaKR
  2. 2.Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, JapanJP
  3. 3.Department of Internal Medicine, University of Ulsan School of Medicine, Seoul, KoreaKR
  4. 4.Department of Internal Medicine, Keimyung University School of Medicine, Taegu, KoreaKR

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