Platelets promote liver regeneration under conditions of Kupffer cell depletion after hepatectomy in mice.
BACKGROUND
Platelets have been proven to promote liver regeneration after hepatectomy. Kupffer cells produce inflammatory cytokines and also promote liver regeneration. In the present study, we examined whether platelets promote liver regeneration after hepatectomy under conditions of Kupffer cell depletion.


METHODS
Seventy percent hepatectomy was carried out in mice, which were subsequently divided into four groups: (1) a normal group without any treatment, (2) a Kupffer cell depleted (KD) group, (3) a thrombocytotic group, and (4) a combined thrombocytotic and Kupffer cell depleted (TKD) group. Growth kinetics in the liver regeneration, growth factors, inflammatory cytokines, and signal transduction relating to hepatocyte proliferation were analyzed.


RESULTS
In the KD group, liver regeneration was significantly delayed compared to the normal group 48 h after hepatectomy. On the other hand, liver regeneration of the TKD group increased significantly compared to KD group, to a level that was the same as that recorded in the normal group. In the thrombocytotic group, liver regeneration increased significantly compared to the normal group. Tumor necrosis factor alpha (TNF-alpha) expression was lower in the KD and TKD groups than in the normal group after hepatectomy, but, in the TKD group, hepatocyte growth factor and Akt phosphorylation were higher than in the normal and KD groups.


CONCLUSIONS
After hepatectomy, liver regeneration in the Kupffer cell depleted group was delayed because of lower TNF-alpha expression. Platelets promote liver regeneration even under condition of Kupffer cell depletion by stimulating hepatocyte growth factor and insulin-like growth factor-1 expression, and they activate Akt.
Murata
Soichiro
S
Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Matsuo
Ryota
R
Ikeda
Osamu
O
Myronovych
Andriy
A
Watanabe
Motonobu
M
Hisakura
Katsuji
K
Nakano
Yoritaka
Y
Hashimoto
Ikuka
I
Ohkohchi
Nobuhiro
N
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D007728:Kupffer Cells / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D013922:Thrombocytosis / Q000503:physiopathology*
D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I