Changes in WNT/beta-catenin pathway during regulated growth in rat liver regeneration.
Changes in WNT/beta-catenin pathway during regulated growth in rat liver regeneration.
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发表时间：
2001
期刊：
影响因子：
13.5
通讯作者：
S. Monga;P. Pediaditakis;K. Mulé;D. Stolz;G. Michalopoulos
中科院分区：
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作者：
S. Monga;P. Pediaditakis;K. Mulé;D. Stolz;G. Michalopoulos
WNT/β-连环蛋白通路在胚胎发生和癌变过程中起重要作用。β-连环蛋白与E-钙粘附素的相互作用在细胞间黏附中起着至关重要的作用。我们利用免疫印迹分析、免疫沉淀研究和免疫荧光技术，报道了70%肝部分切除后大鼠肝再生过程中WNT途径的新发现。我们发现WNT-1和β-连环蛋白主要定位于肝细胞。肝部分切除后，我们观察到在最初的5分钟内，β-连环素蛋白随着移位到细胞核中而开始增加。我们表明，这种增加是由于免疫沉淀研究发现β-连环蛋白降解减少(丝氨酸磷酸化的β-连环蛋白减少)所致。我们观察到由腺瘤性息肉病结肠基因产物(APC)和丝氨酸磷酸化Axin蛋白组成的β-连环蛋白降解复合体在肝切除后5分钟开始激活，导致其水平在这一时间之后下降。在肝再生过程中观察到的E-钙粘蛋白蛋白的定量变化通常与β-连环蛋白的变化相反。此外，使用免疫沉淀法，我们观察到6小时后酪氨酸磷酸化的β-连环蛋白水平升高。因此，WNT途径在调节生长过程中的变化似乎紧密地调节细胞内的β-连环蛋白水平，并可能有助于诱导细胞增殖和靶基因表达。此外，这些变化也可能是为了在肝再生过程中负向调节细胞间的黏附以进行结构重组。
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.