P120 Regulates Beta-catenin Nuclear Translocation Through E-cadherin Endocytosis in Ventilator-induced Lung Injury

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Dec 3

PMID 27911872

Citations 1

Authors

Changping Gu

Chenyang Dai

Yongtao Sun

Mengjie Liu

Yuelan Wang

Xinyi Wu

Affiliations

Soon will be listed here.

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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References

Wang Y, Minshall R, Schwartz D, Hu G . Cyclic stretch induces alveolar epithelial barrier dysfunction via calpain-mediated degradation of p120-catenin. Am J Physiol Lung Cell Mol Physiol. 2011; 301(2):L197-206. PMC: 3154624. DOI: 10.1152/ajplung.00048.2011. View

Cohen T, Lawrence G, Khasgiwala A, Margulies S . MAPK activation modulates permeability of isolated rat alveolar epithelial cell monolayers following cyclic stretch. PLoS One. 2010; 5(4):e10385. PMC: 2860996. DOI: 10.1371/journal.pone.0010385. View

Wu J, Yan Z, Schwartz D, Yu J, Malik A, Hu G . Activation of NLRP3 inflammasome in alveolar macrophages contributes to mechanical stretch-induced lung inflammation and injury. J Immunol. 2013; 190(7):3590-9. PMC: 3608749. DOI: 10.4049/jimmunol.1200860. View

Waschke J, Baumgartner W, Adamson R, Zeng M, Aktories K, Barth H . Requirement of Rac activity for maintenance of capillary endothelial barrier properties. Am J Physiol Heart Circ Physiol. 2003; 286(1):H394-401. DOI: 10.1152/ajpheart.00221.2003. View

Geiger R, Kaufman C, Lam A, Budinger G, Dean D . Tubulin acetylation and histone deacetylase 6 activity in the lung under cyclic load. Am J Respir Cell Mol Biol. 2008; 40(1):76-82. PMC: 2606948. DOI: 10.1165/rcmb.2007-0307OC. View

Liu D, Yan Z, Minshall R, Schwartz D, Chen Y, Hu G . Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2011; 302(4):L370-9. PMC: 3289265. DOI: 10.1152/ajplung.00349.2011. View

Birukova A, Zebda N, Cokic I, Fu P, Wu T, Dubrovskyi O . p190RhoGAP mediates protective effects of oxidized phospholipids in the models of ventilator-induced lung injury. Exp Cell Res. 2010; 317(6):859-72. PMC: 3057230. DOI: 10.1016/j.yexcr.2010.11.011. View

Cohen T, Cavanaugh K, Margulies S . Frequency and peak stretch magnitude affect alveolar epithelial permeability. Eur Respir J. 2008; 32(4):854-61. DOI: 10.1183/09031936.00141007. View

Tremblay L, Miatto D, Hamid Q, Govindarajan A, Slutsky A . Injurious ventilation induces widespread pulmonary epithelial expression of tumor necrosis factor-alpha and interleukin-6 messenger RNA. Crit Care Med. 2002; 30(8):1693-700. DOI: 10.1097/00003246-200208000-00003. View

10.

Koide H, Asai T, Kato H, Yonenaga N, Yokota M, Ando H . Susceptibility of PTEN-positive metastatic tumors to small interfering RNA targeting the mammalian target of rapamycin. Nanomedicine. 2014; 11(1):185-94. DOI: 10.1016/j.nano.2014.09.003. View

11.

Veszelka S, Pasztoi M, Farkas A, Krizbai I, Ngo T, Niwa M . Pentosan polysulfate protects brain endothelial cells against bacterial lipopolysaccharide-induced damages. Neurochem Int. 2006; 50(1):219-28. DOI: 10.1016/j.neuint.2006.08.006. View

12.

Hu G, Malik A, Minshall R . Toll-like receptor 4 mediates neutrophil sequestration and lung injury induced by endotoxin and hyperinflation. Crit Care Med. 2009; 38(1):194-201. PMC: 3739989. DOI: 10.1097/CCM.0b013e3181bc7c17. View

13.

Perez-Moreno M, Davis M, Wong E, Pasolli H, Reynolds A, Fuchs E . p120-catenin mediates inflammatory responses in the skin. Cell. 2006; 124(3):631-44. PMC: 2443688. DOI: 10.1016/j.cell.2005.11.043. View

14.

Iyer S, Ferreri D, DeCocco N, Minnear F, Vincent P . VE-cadherin-p120 interaction is required for maintenance of endothelial barrier function. Am J Physiol Lung Cell Mol Physiol. 2003; 286(6):L1143-53. DOI: 10.1152/ajplung.00305.2003. View

15.

Kaufman C, Geiger R, Dean D . Electroporation- and mechanical ventilation-mediated gene transfer to the lung. Gene Ther. 2010; 17(9):1098-104. PMC: 3483646. DOI: 10.1038/gt.2010.57. View

16.

Dreyfuss D, Ricard J, Saumon G . On the physiologic and clinical relevance of lung-borne cytokines during ventilator-induced lung injury. Am J Respir Crit Care Med. 2003; 167(11):1467-71. DOI: 10.1164/rccm.200206-611CP. View

17.

Ko Y, Yang M, Huang H, Hsu C, Chen L . NF-κB activation in myeloid cells mediates ventilator-induced lung injury. Respir Res. 2013; 14:69. PMC: 3708752. DOI: 10.1186/1465-9921-14-69. View

18.

Nagyoszi P, Wilhelm I, Farkas A, Fazakas C, Dung N, Hasko J . Expression and regulation of toll-like receptors in cerebral endothelial cells. Neurochem Int. 2010; 57(5):556-64. DOI: 10.1016/j.neuint.2010.07.002. View

19.

Dai C, Dai G, Sun Y, Wang Y . Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury. Chin Med J (Engl). 2013; 126(15):2918-22. View

20.

McKechnie S, Drummond G . Cytokines, neurokines or both? Mixed mechanisms of mechanical lung injury. J Physiol. 2010; 588(Pt 11):1813-4. PMC: 2901965. DOI: 10.1113/jphysiol.2010.191478. View