Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury.
BACKGROUND
p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function, but its role has not been explored in alveolar edema induced by ventilation. We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120. We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed, which resulted from the loss of p120.


METHODS
Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor). After the end of stretching for 0, 1, 2, and 4 hours, the cells were lysed, and p120 expression and c-src activation was determined by Western blotting analysis. In vivo, SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg, PEEP = 0, respiratory rate 30-40 betas/min) for 0, 1, 2, and 4 hour and some were pretreated with pp2, and alveolar edema was calculated.


RESULTS
It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells. These changes could be reversed by inhibition of c-src. We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group. Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.


CONCLUSIONS
Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema. Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).
Department of Clinical Medicine of Shandong University, Jinan, Shandong 250012, China.
Chen-yang
CY
Dai
Guo-feng
GF
Dai
Yu
Y
Sun
Yue-lan
YL
Wang
D000818:Animals; D015153:Blotting, Western; D051177:Catenins / Q000502:physiology*; D002478:Cells, Cultured; D051379:Mice; D011650:Pulmonary Alveoli / Q000473:pathology*; D011654:Pulmonary Edema / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000473:pathology*; D000095002:Delta Catenin
D051177:Catenins; D000095002:Delta Catenin