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

Linda E. Greenbaum, Wei Li, Drew E. Cressman, Yong Peng, Gennaro Ciliberto, Valeria Poli, Rebecca Taub

Research output: Contribution to journalArticle

211 Citations (Scopus)

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 β (C/EBPβ) 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/EBPβ in the regenerating liver, we examined the regenerative response after partial hepatectomy in mice that contain a targeted disruption of the C/EBPβ gene. Posthepatectomy, hepatocyte DNA synthesis was decreased to 25% of normal in C/EBPβ -/- mice. The reduced regenerative response was associated with a prolonged period of hypoglycemia that was independent of expression of C/EBPα protein and gluconeogenic genes. C/EBPβ -/- 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/EBPβ -/- livers whereas cyclin D1 expression was normal. The abnormalities in immediate-early gene expression in C/EBPβ -/- livers were distinct from those seen in IL-6 -/- livers. These data link C/EBPβ to the activation of metabolic and growth response pathways in the regenerating liver and demonstrate that C/EBPβ is required for a normal proliferative response.

Original languageEnglish
Pages (from-to)996-1007
Number of pages12
JournalJournal of Clinical Investigation
Volume102
Issue number5
Publication statusPublished - Sep 1 1998

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CCAAT-Enhancer-Binding Proteins
Hepatectomy
Hepatocytes
Liver
Basic-Leucine Zipper Transcription Factors
Protein Splicing
Genes
Cyclin B
Gene Expression
Cyclin E
Protein Tyrosine Phosphatases
Immediate-Early Genes
Cyclin D1
Growth
Mitogen-Activated Protein Kinases
Hypoglycemia
Interleukin-6
Cell Cycle
Transcription Factors

Keywords

  • CCAAT enhancer-binding protein α
  • Cyclin genes
  • Cytokine
  • Hepatic gluconeogenesis
  • Liver regeneration
  • Transcription factor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

CCAAT enhancer-binding protein β is required for normal hepatocyte proliferation in mice after partial hepatectomy. / Greenbaum, Linda E.; Li, Wei; Cressman, Drew E.; Peng, Yong; Ciliberto, Gennaro; Poli, Valeria; Taub, Rebecca.

In: Journal of Clinical Investigation, Vol. 102, No. 5, 01.09.1998, p. 996-1007.

Research output: Contribution to journalArticle

Greenbaum, Linda E. ; Li, Wei ; Cressman, Drew E. ; Peng, Yong ; Ciliberto, Gennaro ; Poli, Valeria ; Taub, Rebecca. / CCAAT enhancer-binding protein β is required for normal hepatocyte proliferation in mice after partial hepatectomy. In: Journal of Clinical Investigation. 1998 ; Vol. 102, No. 5. pp. 996-1007.
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