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Role of transcription factor Ets-1 in the apoptosis of human vascular endothelial cells

✍ Scribed by Kazuhide Teruyama; Mayumi Abe; Toru Nakano; Chika Iwasaka-Yagi; Shoki Takahashi; Shogo Yamada; Yasufumi Sato

Publisher
John Wiley and Sons
Year
2001
Tongue
English
Weight
277 KB
Volume
188
Category
Article
ISSN
0021-9541

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✦ Synopsis

Abstract

Transcription factor Ets‐1 is induced in endothelial cells (ECs) by angiogenic factors, and promotes angiogenesis by inducing angiogenesis‐related genes such as MMPs and integrin β3. Here, we examined the effect of Ets‐1 on apoptosis in ECs. Overexpression of Ets‐1 in human umbilical vein endothelial cells (HUVECs) induced apoptosis under the serum‐deprived condition. VEGF inhibited apoptosis and augmented the DNA binding of Ets‐1 in HUVECs. The inhibition of transcriptional activity of endogenous Ets‐1 by a dominant negative molecule intensified the anti‐apoptotic effect of VEGF. Caspase inhibitors blocked apoptosis of HUVECs induced by Ets‐1. DNA array analysis showed that Ets‐1 up‐regulated pro‐apoptotic genes such as Bid, cytochrome p450, caspase‐4, p27, and p21 more than 2 fold, and down‐regualted anti‐apoptotic genes such as DAD‐1, AXL, Cox‐2, IAP‐2, and MDM‐2 less than 0.5 fold in HUVECs. These results indicate that Ets‐1 itself is pro‐apoptotic to ECs by modulating the expression of apoptosis‐related genes. © 2001 Wiley‐Liss, Inc.

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