Liver-specific loss of β-catenin results in delayed hepatocyte proliferation after partial hepatectomy

Shigeki Sekine, Pedro J.A. Gutiérrez, Billy Yu Ang Lan, Sandy Feng, Matthias Hebrok

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


Recent studies have suggested that β-catenin is involved in the regulation of hepatocyte proliferation in multiple contexts, including organ development and tumorigenesis. We explored the role of β-catenin during liver regeneration using T cell factor/lymphoid enhancer factor (TCF/LEF)-reporter mice (TOPGa1 mice) and liver-specific β-catenin knock-out mice. Liver-specific β-catenin knockout mice showed a delayed onset of DNA synthesis after hepatectomy, whereas recovery of liver mass was not affected. Among putative β-catenin target genes examined, the induction of Ccnd1 expression was reduced, whereas the expression of Myc and Egfr was unaffected. Furthermore, cyclin D1 protein levels were not induced, and the expression of cyclins A, E, and proliferating cell nuclear antigen was delayed. Intriguingly, the analysis of TOPGa1 mice showed that hepatocytes with active TCF/LEF transcription are confined to the pericentral zone and are not increased in number during regeneration, indicating an uncoupling between β-catenin/TCF signaling activity and hepatocyte proliferation. Conclusion: Our results indicate that β-catenin is critical for the proper regulation of hepatocyte proliferation during liver regeneration; however, the activity of β-catenin/TCF signaling does not correlate with hepatocyte proliferation, suggesting that this regulation might be indirect/secondary.

Original languageEnglish
Pages (from-to)361-368
Number of pages8
Issue number2
StatePublished - Feb 2007
Externally publishedYes


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