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Science 312 (5770): 104-107

Copyright © 2006 by the American Association for the Advancement of Science

Platelet-Derived Serotonin Mediates Liver Regeneration

Mickael Lesurtel,1 Rolf Graf,1 Boris Aleil,3 Diego J. Walther,4 Yinghua Tian,1 Wolfram Jochum,2 Christian Gachet,3 Michael Bader,5 Pierre-Alain Clavien1*

Abstract: The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.

1 Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland.
2 Department of Pathology, University Hospital of Zurich, Switzerland.
3 Institut National de la Santé et de la Recherche Médicale 311, Etablissement Français du Sang-Alsace, Strasbourg, France.
4 Max Planck Institute for Molecular Genetics, Berlin, Germany.
5 Max Delbrück Center for Molecular Medicine, Berlin, Germany.

* To whom correspondence should be addressed. E-mail: clavien{at}chir.unizh.ch

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