RGD Reference Report - CCAAT enhancer- binding protein beta is required for normal hepatocyte proliferation in mice after partial hepatectomy. - Rat Genome Database

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

Authors: Greenbaum, LE  Li, W  Cressman, DE  Peng, Y  Ciliberto, G  Poli, V  Taub, R 
Citation: Greenbaum LE, etal., J Clin Invest 1998 Sep 1;102(5):996-1007.
RGD ID: 1300293
Pubmed: PMID:9727068   (View Abstract at PubMed)
PMCID: PMC508965   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI3135   (Journal Full-text)

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.

Objects referenced in this article
Gene CEBPB CCAAT enhancer binding protein beta Homo sapiens
Gene Cebpb CCAAT/enhancer binding protein beta Mus musculus
Gene Cebpb CCAAT/enhancer binding protein beta Rattus norvegicus

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