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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1260-1266.
Prepublished online as a Blood First Edition Paper on April 25, 2006; DOI 10.1182/blood-2005-09-012807.
 Previous Article | Next Article 
Submitted September 7, 2005
Accepted April 4, 2006
Hepatocyte Growth Factor Mediates Angiopoietin-induced
Smooth Muscle Cells Recruitment
Hanako Kobayashi, Laura M DeBusk, Yael O Babichev, Daniel J Dumont, and Pengnian Charles Lin*
Department of Radiation Oncology, Vanderbilt University Medical Center
Department of Cancer Biology,Vanderbilt University Medical Center
Division of Molecular and Cellular Biology Research, Sunnybrook and Women's Research Institute
* Corresponding author; email: charles.lin{at}vanderbilt.edu.
Communication between endothelial cells (ECs) and mural
cells is critical in vascular maturation. Genetic
studies suggest that angiopoietin/Tie2 signaling may
play a role in the recruitment of pericytes or smooth
muscle cells (SMCs) during vascular maturation. However,
the molecular mechanism is unclear. We used microarray
technology to analyze genes regulated by angiopoietin-1
(Ang1), an agonist ligand for Tie2, in endothelial cells
(ECs). We observed that hepatocyte growth factor (HGF),
a mediator of mural cell motility, was upregulated by
Ang1 stimulation. We confirmed this finding by Northern
blot and Western blot in cultured vascular endothelial
cells. Furthermore, stimulation of ECs with Ang1
increased SMC migration toward endothelial cells in a co-
culture assay. Addition of a neutralizing anti-HGF
antibody inhibited the Ang1-induced SMC recruitment,
indicating that the induction of SMC migration by Ang1
was due to the increase of HGF. Very interestingly,
angiopoietin-2 (Ang2), an antagonist ligand of Tie2,
inhibited the Ang1-induced HGF production as well as
Ang1-induced SMC migration. Finally, we showed that
deletion of Tie2 in transgenic mouse reduced HGF
production. Collectively, our data reveal a novel
mechanism of Ang/Tie2 signaling in regulating vascular
maturation and suggest that a delicate balance of Ang1
and Ang2 is critical in this process.
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