Abstract | BACKGROUND/AIMS: 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.
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Authors | Sanae Haga, Wataru Ogawa, Hiroshi Inoue, Keita Terui, Tetsuya Ogino, Rumi Igarashi, Kiyoshi Takeda, Shizuo Akira, Shin Enosawa, Hiroyuki Furukawa, Satoru Todo, Michitaka Ozaki |
Journal | Journal of hepatology
(J Hepatol)
Vol. 43
Issue 5
Pg. 799-807
(Nov 2005)
ISSN: 0168-8278 [Print] Netherlands |
PMID | 16083985
(Publication Type: Journal Article)
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Chemical References |
- STAT3 Transcription Factor
- Serum Albumin
- Stat3 protein, mouse
- Protein Kinases
- mTOR protein, mouse
- Glycogen Synthase Kinase 3 beta
- Gsk3b protein, mouse
- Proto-Oncogene Proteins c-akt
- Ribosomal Protein S6 Kinases, 70-kDa
- TOR Serine-Threonine Kinases
- Glycogen Synthase Kinase 3
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Topics |
- Animals
- Apoptosis
(physiology)
- Cell Proliferation
- Cell Size
- Glycogen Synthase Kinase 3
(metabolism)
- Glycogen Synthase Kinase 3 beta
- Hepatectomy
- Hepatocytes
(cytology, physiology)
- Hypertrophy
- Liver
(anatomy & histology, pathology)
- Liver Regeneration
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Organ Size
- Phosphatidylinositol 3-Kinases
(metabolism)
- Protein Kinases
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Ribosomal Protein S6 Kinases, 70-kDa
(metabolism)
- STAT3 Transcription Factor
(genetics, metabolism)
- Serum Albumin
(metabolism)
- TOR Serine-Threonine Kinases
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