Role of platelets on liver regeneration after 90% hepatectomy in mice.
OBJECTIVE
Mortality after 90% partial hepatectomy in mice was associated with severe acute liver failure. Recently, we revealed that platelets have a strong promotional effect on hepatic regeneration. In the present study, we investigated the effect of thrombocytosis on liver regeneration after 90% hepatectomy in mice.


METHODS
For thrombocytosis induction PEG-rHuMGDF was injected 5 days before operation. Hepatectomy, sparing only the caudate lobe, was performed in normal and thrombocytotic BALB/c mice. Survival rate, platelet number, liver weight/body weight ratio, proliferating cell nuclear antigen, serum parameters, signal transduction and overexpressed genes were examined.


RESULTS
Platelet number was significantly higher in thrombocytotic group. All mice in normal group died within 30 h after hepatectomy. Survival rate in thrombocytotic group was 6/11 at 30 h and 3/11 one week after hepatectomy. Activation of Akt and STAT3 signaling pathways in thrombocytotic group was observed earlier and recognized to be stronger compared to normal group. Cell cycle, signaling pathways, metabolism and transport genes were significantly overexpressed in thrombocytotic group up to 24h after hepatectomy.


CONCLUSIONS
Under the thrombocytotic condition, liver regeneration occurred even in 90% hepatectomized mice. Platelets contribute to cell cycle progression and metabolic pathways in addition to preventing acute liver failure.
Myronovych
Andriy
A
Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Murata
Soichiro
S
Chiba
Mitsuru
M
Matsuo
Ryota
R
Ikeda
Osamu
O
Watanabe
Motonobu
M
Hisakura
Katsuji
K
Nakano
Yoritaka
Y
Kohno
Keisuke
K
Kawasaki
Takuya
T
Hashimoto
Ikuka
I
Shibasaki
Yuki
Y
Yasue
Hiroshi
H
Ohkohchi
Nobuhiro
N
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D023421:Models, Animal; D011092:Polyethylene Glycols; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013922:Thrombocytosis / Q000139:chemically induced / Q000503:physiopathology*; D013926:Thrombopoietin
D018970:Insulin-Like Growth Factor Binding Protein 1; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3