期刊
JOURNAL OF CELL SCIENCE
卷 123, 期 12, 页码 2102-2109出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.070722
关键词
WNT3a; GSK3; beta-catenin; Tcf/Lef; C/EBP-beta; Liver; Pancreas
类别
资金
- Newcastle University
- BBSRC
Developmentally, the pancreas and liver are closely related and pathological conditions-including elevated glucocorticoid levels result in the appearance of hepatocytes in the pancreas. The role of the WNT signalling pathway in this process has been examined in the model transdifferentiating pancreatic acinar AR42J-B-13 (B-13) cell. Glucocorticoid treatment resulted in a transient loss of constitutive WNT3a expression, phosphorylation and depletion of beta-catenin, loss of beta-catenin nuclear localisation, and significant reductions in T-cell factor/lymphoid enhancer factor (Tcf/Lef) transcriptional activity before overt changes in phenotype into hepatocyte-like (B-13/H) cells. A return to higher Tcf/Lef transcriptional activity correlated with the re-expression of WNT3a in B-13/H cells. beta-catenin knock down alone substituted for and enhanced glucocorticoid-dependent transdifferentiation. Overexpression of a mutant beta-catenin (pt-X beta-cat) protein that blocked glucocorticoid-dependent suppression of Tcf/Lef activity resulted in inhibition of transdifferentiation. A small-molecule activator of Tcf/Lef transcription factors blocked glucocorticoid-dependent effects, as observed with pt-X beta-cat expression. Quercetin - a Tcf/Lef inhibitor - did not promote transdifferentiation into B-13/H cells, but did potentiate glucocorticoid-mediated transdifferentiation. These data demonstrate that the transdifferentiation of B-13 cells into hepatocyte-like cells in response to glucocorticoid was dependent on the repression of constitutively active WNT signalling.
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