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Science 299 (5608): 890-893

Copyright © 2003 by the American Association for the Advancement of Science

Angiogenesis-Independent Endothelial Protection of Liver: Role of VEGFR-1

Jennifer LeCouter,1 Dirk R. Moritz,1* Bing Li,2 Gail Lewis Phillips,1 Xiao Huan Liang,1 Hans-Peter Gerber,1 Kenneth J. Hillan,3 Napoleone Ferrara1dagger

The vascular endothelium was once thought to function primarily in nutrient and oxygen delivery, but recent evidence suggests that it may play a broader role in tissue homeostasis. To explore the role of sinusoidal endothelial cells (LSECs) in the adult liver, we studied the effects of vascular endothelial growth factor (VEGF) receptor activation on mouse hepatocyte growth. Delivery of VEGF-A increased liver mass in mice but did not stimulate growth of hepatocytes in vitro, unless LSECs were also present in the culture. Hepatocyte growth factor (HGF) was identified as one of the LSEC-derived paracrine mediators promoting hepatocyte growth. Selective activation of VEGF receptor-1 (VEGFR-1) stimulated hepatocyte but not endothelial proliferation in vivo and reduced liver damage in mice exposed to a hepatotoxin. Thus, VEGFR-1 agonists may have therapeutic potential for preservation of organ function in certain liver disorders.

Departments of 1 Molecular Oncology, 2 Protein Engineering, and 3 Pathology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
*   Present address: Amgen, Alpenquai 30, Post Office Box 2065, CH-6002 Lucerne, Switzerland.

dagger    To whom correspondence should be addressed. E-mail: nf{at}gene.com



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