Tohoku J. Exp. Med., 2001, 194 (1)

Retinoic Acids Repress the Expression of ETS-1 in Endothelial Cells

TAKAYUKI IGARASHI,^1,2 MAYUMI ABE,¹ MANAMI OIKAWA,¹ TOSHIHIRO NUKIWA² and YASUFUMI SATO¹

¹Department of Vascular Biology, and ²Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575

The transcription factor ETS-1 expressed in endothelial cells (ECs) regulates angiogenesis by inducing MMP-1, MMP-3, MMP-9, u-PA and integrin b3 in endothelial cells (ECs). Here, we examined whether anti-angiogenic retinoic acids affect the expression of ETS-1 in ECs. The expression of ets-1 mRNA was up-regulated in sparse to subconfluent ECs and down-regulated in confluent ECs. When confluent ECs were stimulated with basic fibroblast growth factor (bFGF), ets-1 mRNA was induced. All-trans retinoic acid (ATRA) as well as 9-cis retinoic acid reduced the augmented expression of ets-1 mRNA in both subconfluent ECs and bFGF-treated confluent ECs. This inhibitory effect of ATRA was dose dependent and was evident at a concentration as low as 10^–7 M. ATRA did not alter the stability of ets-1 mRNA. Moreover, promoter analysis indicated that ATRA repressed the expression of ets-1 mRNA at transcriptional level. As a result, ATRA reduced the binding of ETS-1 protein to the ETS binding motif. These results indicate that the anti-angiogenic effect of retinoic acids is mediated at least in part by the transcriptional repression of ets-1 mRNA in ECs.

Keywords —— ETS-1; retinoic acid; endothelial cells; angiogenesis

© 2001 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2001, 194, 35-43

Address for reprints: Yasufumi Sato, Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.

e-mail: y-sato@idac.tohoku.ac.jp