原创力文档selective activation of p120ctn-kaiso signaling to unlock contact inhibition of arpe-19 cells without epithelial-mesenchymal transitionp120ctn-kaiso信号的选择性激活解锁arpe-19细胞的接触抑制没有epithelial-mesenchymal过渡.pdfVIP
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selective activation of p120ctn-kaiso signaling to unlock contact inhibition of arpe-19 cells without epithelial-mesenchymal transitionp120ctn-kaiso信号的选择性激活解锁arpe-19细胞的接触抑制没有epithelial-mesenchymal过渡
Selective Activation of p120ctn-Kaiso Signaling to Unlock
Contact Inhibition of ARPE-19 Cells without Epithelial-
Mesenchymal Transition
1,2,3. 1. 1 1
Hung-Chi Chen , Ying-Ting Zhu , Szu-Yu Chen , Scheffer C. G. Tseng *
1Tissue Tech, Inc., Ocular Surface Center, and Ocular Surface Research Education Foundation, Miami, Florida, United States of America, 2 Department of
Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan, 3 Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan,
Taiwan
Abstract
Contact-inhibition ubiquitously exists in non-transformed cells and explains the poor regenerative capacity of in vivo human
retinal pigment epithelial cells (RPE) during aging, injury and diseases. RPE injury or degeneration may unlock mitotic block
mediated by contact inhibition but may also promote epithelial-mesenchymal transition (EMT) contributing to retinal
blindness. Herein, we confirmed that EMT ensued in post-confluent ARPE-19 cells when contact inhibition was disrupted
with EGTA followed by addition of EGF and FGF-2 because of activation of canonical Wnt and Smad/ZEB signaling. In
contrast, knockdown of p120-catenin (p120) unlocked such mitotic block by activating p120/Kaiso, but not activating
canonical Wnt and Smad/ZEB signaling, thus avoiding EMT. Nuclear BrdU labeling was correlated with nuclear release of
Kaiso through p120 nuclear translocation, which was associated with activation of RhoA-ROCK signaling, destabilization of
microtubules. Prolonged p120 siRNA knockdown followed by withdrawal further expanded RPE into more compact
monolayers with a normal phenotype and a higher density. This new str
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