title: Upregulation of the tight junction protein occludin: effects on ventilation-induced lung injury and mechanisms of action.
abstract: BACKGROUND
  Occludin, a tight junction protein, plays an important role in maintaining the integrity of the lung epithelial barrier; however, its role in ventilation-induced lung injury has not been explored. Here, we measured the expression of occludin with different tidal volumes. Our study indicated that the level of occludin was significantly decreased and alveolar permeability was increased owing to acute lung injury.
  
  
  METHODS
  Thirty healthy Wistar rats (15 female, 15 male) weighing 250-300 g, were randomly divided into 5 groups (n = 6 in each group): a control group (group C), a low tidal volume group (group L), a low tidal volume + protein kinase C(PKC) inhibitor group (group L + P), a high tidal volume group (group H) and a high tidal volume + PKC inhibitor group (group H + P). Tracheas of rats in the control group underwent incision without any special treatment. The other four groups were mechanically ventilated for 4 h. The rats in groups L + P and H + P were treated with a PKC inhibitor (bisindolylmaleimide I, 0.12 mg/kg) by intramuscular injection 1 h before anesthesia. Rats were sacrificed after mechanical ventilation. Specimens of lung tissues were harvested. Lung pathological changes were observed using an optical microscope, and lung wet/dry weight ratio was measured. The occludin protein level was assayed by immunohistochemistry and Western blotting.
  
  
  RESULTS
  HE staining and immunohistochemistry results showed that occludin was mainly located in alveolar epithelial cells and some alveolar endothelial cells. The lung injury and alveolar edema were more serious in high tidal volume groups than in low tidal volume groups. Occludin expression was reduced and PKC activation was increased in rats in the high tidal volume groups compared with rats in the low tidal volume groups. Rats that were pretreated with the PKC inhibitor had less pulmonary edema induced by the high tidal volume ventilation.
  
  
  CONCLUSIONS
  Mechanical ventilation can activate the PKC signaling pathway and tight junction proteins participate in this pathway. Up-regulation of occludin can reduce ventilation-induced lung injury.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Liu
authors.forename: Changping
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, Qianfo Mountain Hospital of Shandong University, Jinan 250014, China. wyldgf@163.com.
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D062793:Occludin / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology; D013990:Tidal Volume; D019108:Tight Junctions / Q000378:metabolism*; D015854:Up-Regulation; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D062793:Occludin