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β-Catenin regulation during matrigel-induced rat hepatocyte differentiation

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Abstract

Hepatocytes in primary cultures de-differentiate and re-differentiate following addition of Engelbreth-Holm-Swarm mouse sarcoma (matrigel) to the cultures. The Wnt/β-catenin pathway has been shown to be important in liver growth and development. Here, we investigate changes in β-catenin and its mechanism, during matrigel-induced hepatocyte differentiation. Primary rat hepatocytes were cultured for 8 days, and matrigel was added to half of the cultures. Total and nuclear protein and total RNA were extracted at different days of culture and examined for β-catenin and other Wnt pathway components. A significant increase in total β-catenin protein was observed upon matrigel addition, during hepatocyte differentiation, despite a decrease in β-catenin and frizzled-1 (Wnt receptor) expression. A concurrent decrease in the glycogen synthase kinase-3β (GSK3β), axin, and ser45/thr41-phosphorylated β-catenin proteins was observed in matrigel-treated cultures, implying decreased degradation of β-catenin. Interestingly, a decrease in nuclear β-catenin and total active β-catenin was observed in the presence of matrigel. Matrigel also induced an increased association of β-catenin with Met (hepatocyte growth factor receptor), whereas association with E-cadherin remained unchanged. This coexisted with decreased β-catenin tyrosine phosphorylation. Thus, β-catenin undergoes multifactorial regulation during matrigel-induced hepatocyte differentiation and maturation; this induces its stabilization and membrane translocation, possibly contributing to hepatocyte differentiation.

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Satdarshan P. S. Monga, Amanda Micsenyi, Matt Germinaro, Udayan Apte & Aaron Bell

  2. Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Satdarshan P. S. Monga

  3. University of Pittsburgh Cancer Institute (UPCI)-GI Oncology, McGowan Institute of Regenerative Medicine (MIRM)-Liver, School of Medicine, University of Pittsburgh, S421-BST, 200 Lothrop Street, Pittburgh, PA, 15261, USA

    Satdarshan P. S. Monga

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  1. Satdarshan P. S. Monga
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  2. Amanda Micsenyi
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  3. Matt Germinaro
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  4. Udayan Apte
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  5. Aaron Bell
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Correspondence to Satdarshan P. S. Monga.

Additional information

A. Micsenyi and M. Germinaro contributed equally to this work.

Grant Support: Rango's fund for Enhancement of Pathology Research, American Cancer Society Grant-RSG-03-141-01 and National Institute of Health Grant 1RO1DK62277, to SPSM.

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Monga, S.P.S., Micsenyi, A., Germinaro, M. et al. β-Catenin regulation during matrigel-induced rat hepatocyte differentiation. Cell Tissue Res 323, 71–79 (2006). https://doi.org/10.1007/s00441-005-0045-8

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  • DOI: https://doi.org/10.1007/s00441-005-0045-8

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