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Journal of Biochemistry Advance Access originally published online on November 15, 2007
Journal of Biochemistry 2008 143(2):199-206; doi:10.1093/jb/mvm215
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© 2007 The Japanese Biochemical Society.

BMPs Promote Proliferation and Migration of Endothelial Cells via Stimulation of VEGF-A/VEGFR2 and Angiopoietin-1/Tie2 Signalling

Yuka Suzuki1,*, Kevin Montagne1,2,*, Ayako Nishihara1, Tetsuro Watabe1,{dagger} and Kohei Miyazono1

1Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; and 2INSERM U525, Faculte de medecine Pitie-Salpetriere, Paris, France

{dagger}To whom correspondence should be addressed. Tel: +81-3-5841-3356, Fax: +81-3-5841-3354, E-mail: t-watabe{at}umin.ac.jp

Received September 18, 2007; Accepted October 22, 2007


  Abstract

The differentiation, growth, and survival of endothelial cells (ECs) are regulated by multiple signalling pathways, such as vascular endothelial growth factors (VEGFs) and angiopoietins through their receptor tyrosine kinases, VEGF receptor (VEGFR) 2 and Tie2, respectively. Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)-β family, have been implicated in the development and maintenance of vascular systems. However, their effects on EC proliferation remain to be elucidated. In the present study, we show that BMPs induce the proliferation and migration of mouse embryonic stem cell (ESC)-derived endothelial cells (MESECs) and human microvascular endothelial cells (HMECs). Addition of BMP-4 to culture induced significant proliferation and migration of both types of ECs. BMP-4 also increased the expression and phosphorylation of VEGFR2 and Tie2. These findings suggest that BMP signalling activates endothelium via activation of VEGF/VEGFR2 and Angiopoietin/Tie2 signalling.

Key Words: embryonic stem (ES) cell, Flk1, human microvascular endothelial cell (HMEC), Tie2, VEGFR2

Abbreviations: BMP, bone morphogenetic protein; ECs, endothelial cells; ESC, embryonic stem cell; HMEC, human microvascular endothelial cell; MCs, mural cells; MESEC, mouse embryonic stem cell-derived endothelial cell; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor

*These authors contributed equally to this work.


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