Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration

Bi-Sen Ding, Daniel J. Nolan, Jason M. Butler, Daylon James, Alexander O. Babazadeh, Zev Rosenwaks, Vivek Mittal, Hideki Kobayashi, Koji Shido, David Lyden, Thomas N. Sato, Sina Y. Rabbany and Shahin Rafii ()
Additional contact information
Bi-Sen Ding: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
Daniel J. Nolan: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
Jason M. Butler: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
Daylon James: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
Alexander O. Babazadeh: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
Zev Rosenwaks: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine
Vivek Mittal: Weill Cornell Medical College
Hideki Kobayashi: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
Koji Shido: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
David Lyden: Weill Cornell Medical College
Thomas N. Sato: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan
Sina Y. Rabbany: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College
Shahin Rafii: Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College

Nature, 2010, vol. 468, issue 7321, 310-315

Abstract: Liver regeneration signals There is growing evidence to suggest that endothelial cells are not simply passive conduits for delivering oxygen and nutrients. During embryogenesis, for instance, they induce organogenesis before the circulation has developed. Experiments in a 70% partial hepatectomy liver regeneration model in mice now reveal a molecular pathway by which endothelial cells can sustain liver regeneration after surgical resection. VEGFR2 activation in a defined subpopulation of liver endothelial cells leads to the upregulation of the endothelial-specific transcription factor Id1, which in turn induces the secretion of Wnt2 and hepatocyte growth factor (HGF), which trigger hepatocyte proliferation. This suggests that vascular niche-derived inductive signals that promote liver regeneration could be utilized to initiate and accelerate liver recovery after these surgical procedures.

Date: 2010
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DOI: 10.1038/nature09493

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