Downregulation of Par-3 expression and disruption of Par complex integrity by TGF-beta during the process of epithelial to mesenchymal transition in rat proximal epithelial cells.
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-beta1-induced E-cadherin suppression and alpha-SMA induction. In contrast, knockdown Par-3 expression by siRNA significantly enhanced TGF-beta1-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.
Wang
Xiangyang
X
Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
Nie
Jing
J
Zhou
Qin
Q
Liu
Wei
W
Zhu
Fengxin
F
Chen
Wei
W
Mao
Haiping
H
Luo
Ning
N
Dong
Xiuqing
X
Yu
Xueqing
X
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1