title: Platelet-derived serotonin mediates liver regeneration.
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.
authors.affiliation: Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland.
authors.forename: Mickael
authors.initials: M
authors.lastname: Lesurtel
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.forename: Boris
authors.initials: B
authors.lastname: Aleil
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Walther
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Tian
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002066:Busulfan / Q000494:pharmacology; D049109:Cell Proliferation; D000077144:Clopidogrel; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010976:Platelet Count; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism; D012701:Serotonin / Q000097:blood / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists; D013921:Thrombocytopenia; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D058830:Serotonin 5-HT2 Receptor Antagonists; D012701:Serotonin; D000077144:Clopidogrel; D006916:5-Hydroxytryptophan; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase; D002066:Busulfan; D013988:Ticlopidine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine