Upregulation of the tight junction protein occludin: effects on ventilation-induced lung injury and mechanisms of action.

Mengjie Liu,Mengjie Liu,Yuelan Wang,Changping Gu,Yuelan Wang

doi:10.1186/1471-2466-14-94

Mengjie Liu, Mengjie Liu + Show 3 more

Open Access

https://doi.org/10.1186/1471-2466-14-94

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Abstract

BackgroundOccludin, 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.MethodsThirty 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.ResultsHE 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.ConclusionMechanical 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.

Highlights

Occludin, a tight junction protein, plays an important role in maintaining the integrity of the lung epithelial barrier; its role in ventilation-induced lung injury has not been explored
High VT mediates the decrease in occludin levels and the activation of protein kinase C (PKC) kinase Rats were ventilated for 4 h; the changes in occludin levels and PKC activation were detected by Western blotting at different VT ventilations
The activity of PKC in lung tissue was examined 4 h after Ventilation-induced lung injury (VILI) and the PKCα level was found to be increased in the high VT group compared with the level in the control group (Figure 2)

Summary

Introduction

A tight junction protein, plays an important role in maintaining the integrity of the lung epithelial barrier; its role in ventilation-induced lung injury has not been explored. 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. Ventilation-induced lung injury (VILI) is characterized by increased alveolar–capillary permeability, leading to an influx of protein-rich edema fluid and inflammatory cells into lung alveoli. The root cause for this is that the integrity of the alveolar membrane is damaged. Tight junction (TJ) proteins, including Zo-1, claudin and occludin [1], play an important role in maintaining the integrity

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