Oncotarget

Research Papers: Pathology:

P120 regulates beta-catenin nuclear translocation through E-cadherin endocytosis in ventilator-induced lung injury

Changping Gu, Chenyang Dai, Yongtao Sun, Mengjie Liu, Yuelan Wang _ and Xinyi Wu

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Oncotarget. 2016; 7:83859-83868. https://doi.org/10.18632/oncotarget.13724

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Abstract

Changping Gu1,*, Chenyang Dai2,*, Yongtao Sun1, Mengjie Liu1, Yuelan Wang1 and Xinyi Wu2

1 Department of Anesthesiology, Qianfoshan Hospital of Shandong University, Jinan, Shandong, People’s Republic of China

2 Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Yuelan Wang, email:

Xinyi Wu, email:

Keywords: p120, β-catenin, nuclear translocation, E-cadherin endocytosis, VILI, Pathology Section

Received: May 27, 2016 Accepted: November 21, 2016 Published: November 30, 2016

Abstract

Mechanical stretch induces epithelial barrier dysfunction by altering the location and degradation of cellular junction proteins. p120-catenin (p120) is a cell-cell junction protein known to protect against ventilator-induced lung injury (VILI) that results from improper ventilation of patients. In this study, we sought to determine the role of p120 in VILI and its relationship with the cellular response to mechanical stretch. Mouse lung epithelial cells (MLE-12) transfected with p120 siRNA, p120 cDNA, or E-cadherin siRNA were subjected to 20% cyclic stretch for 2 or 4 hours. Wild-type male C57BL/6 mice were transfected with p120 siRNA-liposome complex to delete p120 in vivo and then subjected to mechanical ventilation. Cyclic stretch induced p120 degradation and the endocytosis of E-cadherin, which induced β-catenin translocation into the nucleus, a key event in lung injury progress and repair. These findings reveal that by reducing β-catenin nuclear translocation through inhibition of E-cadherin endocytosis, p120 protects against ventilator-induced lung injury.


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