title: Role of the PKCα-c-Src tyrosine kinase pathway in the mediation of p120-catenin degradation in ventilator-induced lung injury.
abstract: Ventilator-induced lung injury (VILI) is commonly associated with respiratory barrier dysfunction; however, the mechanisms have not been fully elucidated. This study aimed to determine the order and components of the signalling pathway that mediates the degradation of adherin junction of p120-catenin in VILI.
  
  
  
  For the in vivo study, C57BL/6 mice were pre-treated with inhibitors for 60 min prior to 4 h of mechanical ventilation. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells were pre-treated with inhibitors for 60 min or small interfering RNA (siRNA) for 48 h prior to cyclic stretch at 20% for 4 h. The protein levels of protein kinase Cα (PKCα), activated c-Src and p120-catenin were determined via western blot analysis. Lung injury was determined via HE staining, immunofluorescence, wet/dry ratio and lung injury scores.
  
  
  
  High tidal volume mechanical ventilation and 20% cyclic stretch resulted in the degradation of p120-catenin. Inhibitors of PKCα blocked c-Src kinase activation and p120-catenin degradation in VILI. Inhibitors of c-Src kinase or PP2 or siRNA blocked p120-catenin degradation but not PKCα activation.
  
  
  
  The current findings demonstrates that PKCα and c-Src kinase participate in VILI. PKCα activation phosphorylates c-Src kinase and further decreases p120-catenin in VILI.
authors.affiliation: Department of Anesthesiology, Rizhao People's Hospital, Rizhao, China.|Department of Anesthesiology, Qianfoshan Hospital, Shandong University, Jinan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Rizhao People's Hospital, Rizhao, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Rizhao People's Hospital, Rizhao, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Rizhao People's Hospital, Rizhao, China.
authors.forename: Shengfa
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, Qianfoshan Hospital, Shandong University, Jinan, China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Qianfoshan Hospital, Shandong University, Jinan, China.
authors.forename: Changping
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, Qianfoshan Hospital, Shandong University, Jinan, China. wyldgf@163.com.
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D051177:Catenins / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013990:Tidal Volume / Q000502:physiology; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019061:src-Family Kinases / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C496630:Prkca protein, mouse; D051571:Protein Kinase C-alpha; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse
keywords: c-Src kinase; p120-catenin; phosphorylation; protein kinase Cα; ventilation-induced lung injury