Changes in wnt/β-catenin pathway during regulated growth in rat liver regeneration

被引:230
作者
Monga, SPS
Pediaditakis, P
Mule, K
Stolz, DB
Michalopoulos, GK
机构
[1] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA
关键词
D O I
10.1053/jhep.2001.23786
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The wnt/beta -catenin pathway is important during embryogenesis and carcinogenesis. beta -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 beta -catenin proteins to be predominantly localized in hepatocytes. Immediately following partial hepatectomy, we observed an initial increase in beta -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 beta -catenin (decrease in serine phosphorylated beta -catenin) as seen by immunoprecipitation studies. We observed activation of beta -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 beta -catenin, In addition, using immunoprecipitation, we observe elevated levels of tyrosine-phosphorylated beta -catenin at 6 hours onward. Thus, changes in the wnt pathway during regulated growth seem to tightly regulate cytosolic beta -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.
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页码:1098 / 1109
页数:12
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