Changes in Wnt/β–Catenin Pathway During Regulated Growth in Rat Liver Regeneration

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Abstract
The wnt/β–catenin pathway is important during embryogenesis and carcinogenesis. β–Catenin interaction with E–cadherin has been shown to be crucial in cell–cell adhesion. We report novel findings in the wnt pathway during rat liver regeneration after 70% partial hepatectomy using Western blot analyses, immunoprecipitation studies, and immunofluorescence. We found wnt–1 and β–catenin proteins to be predominantly localized in hepatocytes. Immediately following partial hepatectomy, we observed an initial increase in β–catenin protein during the first 5 minutes with its translocation to the nucleus. We show this increase to be the result of decreased degradation of β–catenin (decrease in serine phosphorylated β–catenin) as seen by immunoprecipitation studies. We observed activation of β–catenin degradation complex comprising of adenomatous polyposis coli gene product (APC) and serine–phosphorylated axin protein, beginning at 5 minutes after hepatectomy, leading to its decreased levels after this time. Quantitative changes observed in E–cadherin protein during liver regeneration are, in general, reverse to those seen in β–catenin. In addition, using immunoprecipitation, we observe elevated levels of tyrosine–phosphorylated β–catenin at 6 hours onward. Thus, changes in the wnt pathway during regulated growth seem to tightly regulate cytosolic β–catenin levels and may be contributing to induce cell proliferation and target gene expression. Furthermore, these changes might also be intended to negatively regulate cell–cell adhesion for structural reorganization during the process of liver regeneration.