Abstract
Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants, which is characterized by alveolar and vascular dysplasia and increased vascular permeability. Hyperoxia is a critical factor in the pathogenesis of BPD, hyperoxia-induced acute lung injury (HALI) model has similar pathological manifestations as human BPD, therefore, may provide insight into the pathogenesis of human BPD. Studies have shown that Twist1 regulates pulmonary vascular permeability of LPS-induced lung injury through the Ang-Tie2 pathway. However, the effect of Twist1 pathway on vascular permeability in HALI has not been reported.Methods: We randomly exposed newborn rats to the room air or hyperoxia for 14 days. Lung histopathology, immunofluorescence, vascular permeability, mRNA and protein expression was assessed on day 1,7,14.Results: Our results verified that hyperoxia caused alveolar and vascular developmental disorders and increased pulmonary vascular permeability, which was consistent with previous findings. In hyperoxia-exposed rat lungs, the expressions of Twist1, Ang1, Tie1, Tie2, and pTie2 were significantly reduced, whereas the expression of Ang2 was significantly increased. Next, we observed a significant down-regulation of the Akt/Foxo1 pathway.Conclusion: In HALI, the pulmonary microvascular permeability was increased, accompanied by changes in Twist1-Tie2 pathway which combined to Angs, and downregulation of Tie1 and Akt/Foxo1 pathway.
Highlights
In the past few decades, the survival rate of preterm infants has increased due to the milder oxygen therapy, prenatal steroids and postpartum pulmonary surfactant (PS), the incidence of the “new” Bronchopulmonary dysplasia (BPD) which is characterized by the alveolar simplification and disordered angiogenesis has increased year by year [1], which has become an essential factor affecting the survival qualityMicrovascular Permeability Mechanism in hyperoxiainduced acute lung injury (HALI) of premature infants
We observed a significant downregulation of the Akt/Foxo1 pathway. These findings suggest that in HALI, the pulmonary microvascular permeability was increased, accompanied by changes in Twist1-Tie pathway which combined to Angs, and downregulation of Tie1 and Akt/Foxo1 pathway, which may play a vital role in microvascular permeability of HALI
We examined the effects of hyperoxia exposure on the levels of Twist1 and Tie receptors in the lung tissues of the newborn rats by IF
Summary
In the past few decades, the survival rate of preterm infants has increased due to the milder oxygen therapy, prenatal steroids and postpartum pulmonary surfactant (PS), the incidence of the “new” BPD which is characterized by the alveolar simplification and disordered angiogenesis has increased year by year [1], which has become an essential factor affecting the survival qualityMicrovascular Permeability Mechanism in HALI of premature infants. Angiogenesis regulation plays a necessary role in the formation of the alveolar-capillary network The deregulation of this process impairs the development of the pulmonary microvascular network and leads to the formation of the immature alveoli, leading to lung pathologies such as BPD [4]. The pathogenesis of BPD is complicated, the hyperoxiainduced acute lung injury (HALI) is a major contributor to the pathogenesis of BPD [5], which is characterized by increased pulmonary permeability and impairment of alveolar development [6]. In HALI, the pulmonary microvascular endothelium is damaged, leaving a bare capillary basement membrane area, resulting in increased permeability of the vascular endothelium [7]. Studies have shown that Twist regulates pulmonary vascular permeability of LPS-induced lung injury through the Ang-Tie pathway. The effect of Twist pathway on vascular permeability in HALI has not been reported
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