beta-Catenin is critical for early postnatal liver growth

Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1578-85. doi: 10.1152/ajpgi.00359.2006. Epub 2007 Mar 1.

Abstract

The Wnt/beta-catenin pathway plays an important role in embryonic liver development, morphogenesis, and organogenesis. Here, we report on the activation of beta-catenin during early postnatal liver growth. Modulation of beta-catenin expression was studied in CD-1 mice livers over a time course of 0 to 30 postnatal days (PD) and 3 mo. Increases in total and active beta-catenin were observed in developing livers from PD 5 to 20. A concomitant increase in the beta-catenin-transcription factor (TCF) complex along with nuclear and cytoplasmic beta-catenin was also evident, which coincided with ongoing hepatocyte proliferation by PCNA immunohistochemistry. This activation of beta-catenin was multifactorial, including cyclical inhibition of glycogen synthase kinase-3beta, suppression of casein kinase-IIalpha, and a transient increase in beta-catenin gene expression. Coprecipitation experiments revealed the formation of the beta-catenin-cadherin complex at PD 5, whereas adequate beta-catenin-c-Met complex at the hepatocyte membrane did not form until PD 20, which might be contributing to the free beta-catenin pool during early postnatal growth. Furthermore, beta-catenin liver-specific knockout mice exhibited smaller livers at PD 30, secondary to diminished hepatocyte proliferation. These data indicate that the activation of beta-catenin is critical for early postnatal liver growth and development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Casein Kinase II / metabolism
  • Cell Membrane / metabolism
  • Cell Proliferation*
  • Gene Expression Regulation, Developmental
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism*
  • Liver / cytology
  • Liver / enzymology
  • Liver / growth & development
  • Liver / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-met / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction* / genetics
  • TCF Transcription Factors / metabolism
  • Time Factors
  • Wnt Proteins / metabolism*
  • beta Catenin / deficiency
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, mouse
  • Cadherins
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • TCF Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • Proto-Oncogene Proteins c-met
  • Casein Kinase II
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3