期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1782, 期 1, 页码 51-59出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2007.11.002
关键词
Par-3; Par complex; cell junction; epithelial to mesenchymal transition; TGF-beta 1; proximal epithelial cell
Epithelial to mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis and the initial step is disruption of cell junction and cell polarity. TGF-beta has been demonstrated as the most important mediator of EMT which is sufficient to initiate and complete the whole course of EMT, however, the detailed mechanism of TGF-beta in modulating the disruption of cell junction still remains unclear. Par-3 is a component of Par complex which plays a crucial role in the establishment and maintenance of epithelial polarity. In this study, we found that TGF-beta treatment resulted in a dose- and time-dependent downregulation of Par-3 protein together with the suppression of E-cadherin expression and induction of alpha-SMA. The decreased Par-3 subsequently resulted in the redistribution of Par-6-aPKC complex from cell membrane to cytoplasm. Forced expression of exogenous Par-3 into rat proximal epithelial cells (NRK52E) led to a drastic blockage of TGF-beta 1-induced E-cadherin suppression and alpha-SMA induction. In contrast, knockdown Par-3 expression by siRNA significantly enhanced TGF-beta 1-induced E-cadherin suppression and alpha-SMA induction. These data indicate that downregulation of Par-3 and subsequent disruption of Par complex integrity might be one mechanism that TGF-beta destroys cell polarity during EMT. (C) 2007 Elsevier B.V. All rights reserved.
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