Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model

Hiroshi Murata, Takahito Yagi, Hiromi Iwagaki, Tetsuya Ogino, Hiroshi Sadamori, Hiroyoshi Matsukawa, Yuzoh Umeda, Sanae Haga, Noriaki Takaka, Michitaka Ozaki

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background and Aim: 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.

Original languageEnglish
Pages (from-to)2173-2180
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Fatty liver
  • Hepatectomy
  • Liver regeneration
  • STAT3
  • Wee1/Myt1

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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