Downregulation of Par-3 expression and disruption of Par complex integrity by TGF-β during the process of epithelial to mesenchymal transition in rat proximal epithelial cells

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1782

Article

Wang, Xiangyang¹  Nie, Jing¹  Zhou, Qin¹  Liu, Wei¹  Zhu, Fengxin¹  Chen, Wei¹  Mao, Haiping¹  Luo, Ning¹  Dong, Xiuqing¹  Yu, Xueqing¹ 

[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Nephrol, Guangzhou 510080, Peoples R China

关键词: Par-3;    Par complex;    cell junction;    epithelial to mesenchymal transition;    TGF-beta 1;    proximal epithelial cell;   

DOI  :  10.1016/j.bbadis.2007.11.002

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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