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Platelet-derived serotonin mediates liver regeneration

Official URL:https://doi.org/10.1126/science.1123842
PubMed:View item in PubMed
Creators Name:Lesurtel, M. and Graf, R. and Aleil, B. and Walther, D.J. and Tian, Y. and Jochum, W. and Gachet, C. and Bader, M. and Clavien, P.A.
Journal Title:Science
Journal Abbreviation:Science
Volume:312
Number:5770
Page Range:104-107
Date:7 April 2006
Keywords:5-HT2A Serotonin Receptor, 5-HT2B Serotonin Receptor, 5-Hydroxytryptophan, Amphetamines, Blood Platelets, Busulfan, Cell Proliferation, Hepatectomy, Hepatocytes, Inbred C57BL Mice, Knockout Mice, Liver, Platelet Count, Serotonin, Serotonin 5-HT2 Receptor Antagonists, Thrombocytopenia, Ticlopidine, Tryptophan Hydroxylase, Animals, Mice
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
ISSN:0036-8075
Publisher:American Association for the Advancement of Science (U.S.A.)
Item Type:Article

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