Activation of c-Src tyrosine kinase mediated the degradation of occludin in ventilator-induced lung injury

Respiratory Research

Yuelan Wang²  Xin Wang¹  Changping Gu²  Mengjie Liu²  Tao Zhao² 

[1] Department of Anesthesiology, Jinan Fifth People’s Hospital, Ji’nan, Shandong, China;Department of Anesthesiology, Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan 250014, Shandong Province, China

关键词: c-Src inhibitor;    Occludin;    Tight junctions;    Ventilation-induced lung injury;   

Others  :  1137224
DOI  :  10.1186/s12931-014-0158-2

 received in 2014-08-12, accepted in 2014-11-25,  发布年份 2014

【 摘 要 】

Background

Ventilator-induced lung injury (VILI) is characterized by increased alveolar permeability, pulmonary edema. The tyrosine kinase, c-Src, is involved in VILI but its role has not been fully elucidated. This study examined the relationship between c-Src activation and occludin levels in VILI both in vitro and in vivo.

Methods

For the in vivo study, Wistar rats were randomly divided into five groups: control (group C); normal tidal volume (group M); normal tidal volume + c-Src inhibitor (PP2) (group M + P); high tidal volume (group H); and high tidal volume + c-Src inhibitor (PP2) (group H + P). Rats in all groups but group C underwent mechanical ventilation for 4 h. For the in vitro study, MLE-12 cells pretreated with PP2 and siRNA underwent cyclic stretching at 8% or 20% for 0, 1, 2 and 4 h. The expressions of occludin, c-Src, and p-c-Src were analyzed by western blotting, hematoxylin and eosin (HE) staining, and immunofluorescence.

Results

For the in vivo study, rats in group H showed decreased occludin expression and activated c-Src compared with group C. HE staining and lung injury score showed more severe lung injury and alveolar edema in group H compared with group M and group C. Group H + P had less pulmonary edema induced by the high tidal volume ventilation. For the in vitro study, occludin expression decreased and c-Src activation increased as indicated by the phosphorylation of c-Src over time. Consistently, PP2 could restore occludin levels.

Conclusions

Mechanical ventilation can activate c-Src by phosphorylation and increase the degradation of occludin. c-Src inhibitor can ameliorate barrier function and lung injury by up-regulating occludin.

【 授权许可】

   
2014 Zhao et al.; licensee BioMed Central Ltd.

【 图 表 】

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