Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model.
OBJECTIVE
The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH).


METHODS
db/db fatty mice and lean littermates were used for the experiments. Following 70% PH, the survival rate and recovery of liver mass were examined. Liver tissue was histologically examined and analyzed by western blotting and RT-PCR.


RESULTS
Of 35 db/db mice, 25 died within 48 h of PH, while all of the control mice survived. Liver regeneration of surviving db/db mice was largely impaired. In db/db mice, mitosis of hepatocytes after PH was disturbed, even though proliferating cell nuclear antigen (PCNA) expression (G1 to S phase marker) in hepatocytes was equally observed in both mice groups. Interestingly, phosphorylation of Cdc2 in db/db mice was suppressed by reduced expression of Wee1 and Myt1, which phosphorylate Cdc2 in S to G2 phase.


CONCLUSIONS
In steatotic liver, cell-cycle-related proliferative disorders occurred at mid-S phase after PCNA expression. Reduced expression of Wee1 and Myt1 kinases may therefore maintain Cdc2 in an unphosphorylated state and block cell cycle progression in mid-S phase. These kinases may be critical factors involved in the impaired liver regeneration in fatty liver.
Murata
Hiroshi
H
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, Shikata, Okayama, Japan.
Yagi
Takahito
T
Iwagaki
Hiromi
H
Ogino
Tetsuya
T
Sadamori
Hiroshi
H
Matsukawa
Hiroyoshi
H
Umeda
Yuzoh
Y
Haga
Sanae
S
Takaka
Noriaki
N
Ozaki
Michitaka
M
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA; D005234:Fatty Liver / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006498:Hepatectomy / Q000379:methods*; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008938:Mitosis; D010766:Phosphorylation; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015996:Survival Rate
D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D004247:DNA