title: P120 regulates beta-catenin nuclear translocation through E-cadherin endocytosis in ventilator-induced lung injury.
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.
authors.affiliation: Department of Anesthesiology, Qianfoshan Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Changping
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Anesthesiology, Qianfoshan Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Qianfoshan Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Qianfoshan Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D040542:Mechanotransduction, Cellular; D008810:Mice, Inbred C57BL; D059748:Proteolysis; D034622:RNA Interference; D012121:Respiration, Artificial / Q000009:adverse effects*; D013997:Time Factors; D014162:Transfection; D055397:Ventilator-Induced Lung Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D051176:beta Catenin / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051177:Catenins; D051176:beta Catenin; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse
keywords: E-cadherin endocytosis; Pathology Section; VILI; nuclear translocation; p120; β-catenin