Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice
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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STAT3 was dispensable for liver development.
“Furthermore, it was reported that STAT3 was dispensable for liver development.33”
From Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers (2023) · cites this paper as [33]
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“STAT3 was first described based on the DNA-binding activity of IL-6-stimulated hepatocytes, capable of selectively interacting with an enhancer element in the promoter of acute-phase genes, known as acute-phase response elements [15–17].”
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Self-citationSTAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration
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“In liver-specific STAT3-KO (LS3-KO) mice, no abnormalities of liver development or structure were observed, but they showed reduced mitogenic response following PH [19].”
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Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics
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Autonomic regulation of liver regeneration after partial hepatectomy in mice
Ikeda, O., Ozaki, M., Murata, S., Matsuo, R., Nakano, Y., Watanabe, M., Hisakura, K., Myronovych, A., Kawasaki, T., Kohno, K., et al. (2009) · Journal of Surgical Research · doi:10.1016/j.jss.2008.02.059 · Cited by 32 · see citing works
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- Authors
- Haga, S., Ogawa, W., Inoue, H., Terui, K., Ogino, T., Igarashi, R., Takeda, K., Akira, S., Enosawa, S., Furukawa, H., Todo, S., & Ozaki, M.
- Affiliations
- Hokkaido University (JP)
- Kobe University (JP)
- Chiba University (JP)
- Okayama University (JP)
- Kyushu University (JP)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- National Research Institute for Child Health and Development (JP)
- Corresponding author
- Ozaki, Michitaka
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 43
- Issue
- 5
- Pages
- 799-807
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2089019762
- Cited by
- 108
- References
- 3
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 7 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 9 · 2012: 8
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- liver regeneration, partial hepatectomy, hepatocyte hypertrophy, hepatocyte proliferation, STAT3 deficiency, Akt signaling, PI3K/Akt signaling, mTOR, GSK3β, p70S6K, cyclin D1, dominant-negative Akt
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Hepatectomy, Hypertrophy, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Organ Size, Protein Kinases, Serum Albumin, Apoptosis, Mice, Knockout, Phosphatidylinositol 3-Kinases, Hepatocytes, Glycogen Synthase Kinase 3, Ribosomal Protein S6 Kinases, 70-kDa, Cell Size, Cell Proliferation, STAT3 Transcription Factor, Proto-Oncogene Proteins c-akt, Mice, TOR Serine-Threonine Kinases
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