on March 18, 2004
Published online before print March 18, 2004, doi: 10.1161/01.ATV.0000126373.52450.32
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Submitted on January 8, 2004
Accepted on February 25, 2004
Vascular Endothelial Zinc Finger 1 Is Involved in the Regulation of Angiogenesis: Possible Contribution of Stathmin/OP18 as a Downstream Target Gene
Hiroki Miyashita ;
From the Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
* To whom correspondence should be addressed. E-mail: y-sato{at}idac.tohoku.ac.jp.
Objective--Vascular endothelial zinc finger 1 (Vezf1) is a recently identified zinc finger transcription factor that is expressed in endothelial cells (ECs) during vascular development in mouse embryo. Here, we present that Vezf1 was expressed in ECs at the site of postnatal angiogenesis. We therefore examined whether Vezf1 was involved in the regulation of angiogenesis.
Methods and Results--The specific downregulation of Vezf1 by antisense oligodeoxynucleotide (AS-ODN) significantly inhibited the proliferation, migration, and network formation of cultured ECs as well as angiogenesis in vivo. Vezf1 AS-ODN downregulated the expression of stathmin/oncoprotein18 (OP18), a microtubule-destabilizing protein, in ECs, whereas transient transfection of Vezf1 cDNA increased the expression of stathmin/OP18 in ECs. To explore the relationship between Vezf1 and stathmin/OP18, we specifically downregulated stathmin/OP18. We found that stathmin/OP18 AS-ODN inhibited the proliferation, migration, and network formation of ECs as Vezf1 AS-ODN did. Moreover, Vezf1 AS-ODN decreased G2/M population of ECs and increased apoptosis, which reproduced the characteristic feature of stathmin/OP18 inhibition.
Conclusion--These results suggest that Vezf1 is involved in the regulation of angiogenesis, at least in part, through the expression of stathmin/OP18 in ECs.
Key words: Vezf1 • transcription factor • endothelial cell • angiogenesis • stathmin/OP18
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