β-catenin is critical for early postnatal liver growth
β-catenin is critical for early postnatal liver growth
复制标题
DOI：
10.1152/ajpgi.00359.2006
复制
发表时间：
2007-06-01
影响因子：
4.5
通讯作者：
Monga, Satdarshan P. S.
中科院分区：
文献类型：
--
作者：
Apte, Udayan;Zeng, Gang;Monga, Satdarshan P. S.
Wnt/β-连环蛋白通路在胚胎肝脏发育、形态发生和器官发生中起重要作用。在这里，我们报告在出生后早期肝脏生长过程中β-连环蛋白的激活。在出生后0 - 30天（PD）和3个月的时间过程中，在CD-1小鼠肝脏中研究了β-连环蛋白表达的调节。从PD 5至20，在发育中的肝脏中观察到总β-连环蛋白和活性β-连环蛋白增加。伴随的β-连环蛋白-转录因子（TCF）复合物沿着细胞核和细胞质β-连环蛋白的增加也是明显的，这与PCNA免疫组化显示的持续肝细胞增殖相一致。β-连环蛋白的激活是多因素的，包括糖原合成酶激酶-3 β的周期性抑制、酪蛋白激酶-II α的抑制和β-连环蛋白基因表达的瞬时增加。共沉淀实验显示，在PD 5时形成β-连环蛋白-钙粘蛋白复合物，而在PD 20时才在肝细胞膜上形成足够的β-连环蛋白-c-Met复合物，这可能有助于出生后早期生长过程中的游离β-连环蛋白库。此外，β-连环蛋白肝特异性敲除小鼠在PD 30时表现出较小的肝脏，继发于肝细胞增殖减少。这些数据表明，β-连环蛋白的激活对出生后早期肝脏的生长和发育至关重要。
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-3 beta , suppression of casein kinase-II alpha, 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 liverspecific 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.