title: Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice.
abstract: OBJECTIVE
  Liver regeneration following hepatectomy is complicated and involves a variety of interacting factors. The present study was designed to study the roles of proliferation and hypertrophy of hepatocytes in liver regeneration following hepatectomy in liver-specific STAT3-knockout (LS3-KO) mice lacking mitogenic activity.
  
  
  METHODS
  Partial hepatectomy was performed in LS3-KO and control mice. Liver regeneration was estimated by the liver weight, cell proliferation and cell size, and the related cellular signals were analyzed.
  
  
  RESULTS
  Proliferation of hepatocytes following PH was markedly suppressed in LS3-KO mice with reduced cyclinD1 transcript. However, liver mass recovered sufficiently following PH in LS3-KO mice almost equal to that of control mice. Analysis of hepatocellular growth revealed that cell size following hepatectomy was significantly larger in LS3-KO mice than in control mice. Hepatectomy induced immediate but transient phosphorylation of Akt, p70S6K, mTOR and GSK-3beta in LS3-KO mice much more than in control mice. Additionally, adenoviral transfection of dominant negative mutant of Akt to control and LS3-KO mice led to insufficient liver regeneration following hepatectomy.
  
  
  CONCLUSIONS
  PI3-K/Akt-mediated responsive hepatocellular hypertrophy may be essential for liver regeneration following hepatectomy and sufficiently compensated liver regeneration even in STAT3-deficient liver, in which cell proliferation is impaired.
authors.affiliation: Department of Surgery, Hokkaido University Graduate School of Medicine, Faculty of Medicine, Sapporo, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Haga
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Keita
authors.initials: K
authors.lastname: Terui
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogino
authors.forename: Rumi
authors.initials: R
authors.lastname: Igarashi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Shin
authors.initials: S
authors.lastname: Enosawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D006984:Hypertrophy; D008099:Liver / Q000033:anatomy & histology / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
chemical_list: D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D050796:STAT3 Transcription Factor; D012709:Serum Albumin; D058570:TOR Serine-Threonine Kinases; C494087:Stat3 protein, mouse; C546843:mTOR protein, mouse; C000605507:Gsk3b protein, mouse