Platelet-derived serotonin mediates liver regeneration.
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.
Lesurtel
Mickael
M
Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland.
Graf
Rolf
R
Aleil
Boris
B
Walther
Diego J
DJ
Tian
Yinghua
Y
Jochum
Wolfram
W
Gachet
Christian
C
Bader
Michael
M
Clavien
Pierre-Alain
PA
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
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