title: Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model.
abstract: 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.
authors.affiliation: Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, Shikata, Okayama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murata
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwagaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsukawa
authors.forename: Yuzoh
authors.initials: Y
authors.lastname: Umeda
authors.forename: Sanae
authors.initials: S
authors.lastname: Haga
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takaka
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
mesh_terms: 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
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D004247:DNA