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Blood, 1 July 2004, Vol. 104, No. 1, pp. 166-169.
Prepublished online as a Blood First Edition Paper on March 16, 2004; DOI 10.1182/blood-2003-09-3293.


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Submitted September 25, 2003
Accepted March 1, 2004

Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells

Yasuhiro Suzuki, Yusuke Komi, Hiromi Ashino, Jun Yamashita, Jun Inoue, Atsushi Yoshiki, Anne Eichmann, Hiroshi Amanuma, and Soichi Kojima*

Mol Cell Pathol Res Unit, RIKEN, Wako, Saitama, Japan
Dept Mol Biol, Tokyo Met Inst Med Sci, Bunkyo-ku, Tokyo, Japan
Stem Cell Res Ctr, Kyoto Univ, Sakyo-ku, Kyoto, Japan
ANB Tsukuba Inst, ALOKA Co. Ltd, Niihari, Ibaraki, Japan
Exp Animal Division, RIKEN BioResource Ctr, Tsukuba, Ibaraki, Japan
INSERM U36, College de France, Berthelot, Paris, France
Mol Cell Sci, RIKEN, Wako, Saitama, Japan
Mol Cell Pathol Res Unit, RIKEN, Wako, Saitama, Japan; Mol Cell Sci, RIKEN, Wako, Saitama, Japan

* Corresponding author; email: skojima{at}postman.riken.go.jp.

Inhibition by all-trans retinoic acid (atRA) of the microvasculature formation in chicken chorioallantoic membrane (CAM) accompanied remarkably reduced numbers of endothelial cells (ECs) and increased numbers of mural cells (MCs) under the chorionic epithelial layer. Ro41-5253 (retinoid antagonist) exerted the opposite effect. Although atRA did not affect the differentiation of murine embryonic stem cell-derived vascular progenitor cells (VPCs) into ECs or MCs, atRA suppressed EC-MC interaction, leading to impaired branching. In both atRA-treated VPC cultures and CAM tissues underneath the chorionic epithelial layer, the expression of angiopoietin-2 (Ang-2; competitor for Ang-1) was enhanced, whereas that of Tie2 (a receptor for Angs) was reduced. Simultaneous treatment with Ang-1 partially blocked RA induction of EC-MC malinteraction and reduction in blood vessel formation. These results suggest that retinoid(s) may reduce EC-MC interaction by down-regulating Tie2 signaling as well as decreased EC numbers, which lead to impaired vascular remodeling.


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