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Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration

Author

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  • 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
    Bioengineering Program, Hofstra University, Hempstead, New York 11549, USA)

  • Shahin Rafii

    (Howard Hughes Medical Institute, Ansary Stem Cell Institute, Weill Cornell Medical College)

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.

Suggested Citation

  • 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 , 2010. "Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration," Nature, Nature, vol. 468(7321), pages 310-315, November.
    • Handle: RePEc:nat:nature:v:468:y:2010:i:7321:d:10.1038_nature09493
    DOI: 10.1038/nature09493
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    Cited by:

    1. Germán Belenguer & Gianmarco Mastrogiovanni & Clare Pacini & Zoe Hall & Anna M. Dowbaj & Robert Arnes-Benito & Aleksandra Sljukic & Nicole Prior & Sofia Kakava & Charles R. Bradshaw & Susan Davies & M, 2022. "RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Hirotoki Ohkubo & Yoshiya Ito & Tsutomu Minamino & Koji Eshima & Ken Kojo & Shin-ichiro Okizaki & Mitsuhiro Hirata & Masabumi Shibuya & Masahiko Watanabe & Masataka Majima, 2014. "VEGFR1-Positive Macrophages Facilitate Liver Repair and Sinusoidal Reconstruction after Hepatic Ischemia/Reperfusion Injury," PLOS ONE, Public Library of Science, vol. 9(8), pages 1-14, August.
    3. Linda Große-Segerath & Paula Follert & Kristina Behnke & Julia Ettich & Tobias Buschmann & Philip Kirschner & Sonja Hartwig & Stefan Lehr & Mortimer Korf-Klingebiel & Daniel Eberhard & Nadja Lehwald-T, 2024. "Identification of myeloid-derived growth factor as a mechanically-induced, growth-promoting angiocrine signal for human hepatocytes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Cyrill Géraud & Konstantin Evdokimov & Beate K Straub & Wiebke K Peitsch & Alexandra Demory & Yvette Dörflinger & Kai Schledzewski & Astrid Schmieder & Peter Schemmer & Hellmut G Augustin & Peter Schi, 2012. "Unique Cell Type-Specific Junctional Complexes in Vascular Endothelium of Human and Rat Liver Sinusoids," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-12, April.

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