Cited by 270Liver physiology and pathologyOrgan Transplantation Techniques and OutcomesTissue Engineering and Regenerative Medicine

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CCAAT enhancer- binding protein beta is required for normal hepatocyte proliferation in mice after partial hepatectomy.

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Greenbaum, L E, Li, W, Cressman, D E, Peng, Y, Ciliberto, G, Poli, V, Taub, R·1998·Journal of Clinical Investigation

DOI 10.1172/jci3135PMC PMC508965

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Abstract

After two-thirds hepatectomy, normally quiescent liver cells are stimulated to reenter the cell cycle and proliferate to restore the original liver mass. The level of bZIP transcription factor CCAAT enhancer-binding protein beta (C/EBPbeta) increases in the liver during the period of cell proliferation. The significance of this change in C/EBP expression is not understood. To determine the role of C/EBPbeta in the regenerating liver, we examined the regenerative response after partial hepatectomy in mice that contain a targeted disruption of the C/EBPbeta gene. Posthepatectomy, hepatocyte DNA synthesis was decreased to 25% of normal in C/EBPbeta -/- mice. The reduced regenerative response was associated with a prolonged period of hypoglycemia that was independent of expression of C/EBPalpha protein and gluconeogenic genes. C/EBPbeta -/- livers showed reduced expression of immediate-early growth-control genes including the Egr-1 transcription factor, mitogen-activated protein kinase protein tyrosine phosphatase (MKP-1), and HRS, a delayed-early gene that encodes an mRNA splicing protein. Cyclin B and E gene expression were dramatically reduced in C/EBPbeta -/- livers whereas cyclin D1 expression was normal. The abnormalities in immediate-early gene expression in C/EBPbeta -/- livers were distinct from those seen in IL-6 -/- livers. These data link C/EBPbeta to the activation of metabolic and growth response pathways in the regenerating liver and demonstrate that C/EBPbeta is required for a normal proliferative response.

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Authors: Greenbaum, L. E., Li, W., Cressman, D. E., Peng, Y., Ciliberto, G., Poli, V, & Taub, R.
Affiliations: University of Pennsylvania (US)
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
University of Dundee (GB)
ORCID: Peng, Y
Ciliberto, G
Poli, V
Taub, R
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1998-09-01
Volume: 102
Issue: 5
Pages: 996-1007
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci3135
PMC: PMC508965
OpenAlex: W2055209830
Cited by: 270
References: 72
Citations by year: 2026: 1 · 2025: 2 · 2024: 3 · 2023: 10 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 6 · 2016: 3 · 2015: 8 · 2014: 6 · 2013: 7 · 2012: 5
FWCI: 12.28
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders: National Institutes of Health (K08 DK, 5r01dk049629-05)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK044237, DK 44237, DK-49629, P01DK049210, DK 49210)
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: C/EBPβ, hepatocyte proliferation, liver regeneration, partial hepatectomy, knockout mice, hypoglycemia, immediate early genes, EGR1, MKP-1, Hrs, cyclin B, cyclin E, cyclin D1, bZIP transcription factors, DNA synthesis
MeSH terms: Animals, Cell Division, Cells, Cultured, DNA, DNA-Binding Proteins, Gene Expression Regulation, Gluconeogenesis, Hepatectomy, Immunohistochemistry, Liver Regeneration, Nuclear Proteins, Phosphoproteins, RNA Splicing, RNA, Messenger, Transcription Factors, Trans-Activators, S Phase, Cyclins, Mice, Knockout, CCAAT-Enhancer-Binding Proteins, STAT3 Transcription Factor, Mice, Endosomal Sorting Complexes Required for Transport

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CCAAT enhancer- binding protein beta is required for normal hepatocyte proliferation in mice after partial hepatectomy.

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