期刊
CELL AND TISSUE RESEARCH
卷 323, 期 1, 页码 71-79出版社
SPRINGER
DOI: 10.1007/s00441-005-0045-8
关键词
Wnt; liver; development; cancer; HGF/Met; cell culture (rat hepatocytes)
类别
资金
- NIDDK NIH HHS [1R01DK62277] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK062277] Funding Source: NIH RePORTER
Hepatocytes in primary cultures de-differentiate and re-differentiate following addition of Engelbreth-Holm-Swarm mouse sarcoma (matrigel) to the cultures. The Wnt/beta-catenin pathway has been shown to be important in liver growth and development. Here, we investigate changes in beta-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 beta-catenin and other Wnt pathway components. A significant increase in total beta-catenin protein was observed upon matrigel addition, during hepatocyte differentiation, despite a decrease in beta-catenin and frizzled-1 (Writ receptor) expression. A concurrent decrease in the glycogen synthase kinase-3 beta (GSK3 beta), axin, and ser45/thr41-phosphorylated beta-catenin proteins was observed in matrigel-treated cultures, implying decreased degradation of beta-catenin. Interestingly, a decrease in nuclear beta-catenin and total active beta-catenin was observed in the presence of matrigel. Matrigel also induced an increased association of beta-catenin with Met (hepatocyte growth factor receptor), whereas association with E-cadherin remained unchanged. This coexisted with decreased beta-catenin tyrosine phosphorylation. Thus, beta-catenin undergoes multifactorial regulation during matrigel-induced hepatocyte differentiation and maturation; this induces its stabilization and membrane translocation, possibly contributing to hepatocyte differentiation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据