Effect of intermittent hypoxia or hyperoxia on lung development in preterm rat neonates during constant oxygen therapy

Wang, Juanmei; Zhang, Aimin; Li, Yun; Huang, Furong; Zhao, Ming‐Hui; Wu, Bufei; He, Shijun

doi:10.1002/jcb.29019

Cited by 12 publications

(13 citation statements)

References 29 publications

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“…In postnatal lung developing, HIF-1α similarly increases vasculature growth and alveolar maturation 17 . As expected, HIF-1α stabilization preserves alveolar and vascular growth in the BPD model 18 . In contrast, HIF-1α deficiency reduces lung morphogenesis 19 .…”

Section: Introductionsupporting

confidence: 83%

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

Jin

Gao

Yin

et al. 2022

Laboratory Investigation

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Bronchopulmonary dysplasia (BPD) is the most common challenge in preterm neonates. Retardation of alveolar development characterizes the pulmonary pathology in BPD. In the present study, we explored the roles of the CD146-HIF-1α axis in BPD. We demonstrated that the levels of reactive oxygen species (ROS) and soluble CD146 (sCD1146) were increased in the peripheral blood of preterm neonates with BPD. In alveolar epithelial cells, hyperoxia promoted the expression of HIF-1α and CD146, which reinforced each other. In a mouse model of BPD, by exposing pups to 65% hyperoxia, HIF-1α and CD146 were increased in the pulmonary tissues. Mechanistically, CD146 hindered the migration of alveolar epithelial cells; in contrast, movement was significantly enhanced in CD146-knockout alveolar epithelial cells. As expected, CD146-knockout ameliorated alveolarization and improved BPD disease severity. Taken together, our findings imply that the CD146-HIF-1α axis contributes to alveolarization and that CD146 may be a novel candidate in BPD therapy.

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Section: Introductionsupporting

confidence: 83%

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

Jin

Gao

Yin

et al. 2022

Laboratory Investigation

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“…In further studies in rats, only hyperoxia with intermittent hypoxia decreased the antioxidative capacities in the lung and lung injury. The inhibition of ROS preceded the influx of inflammatory cells and prohibited lung injury [ 37 , 39 ]. These data allow the conclusion that approaches towards preventing ROS-induced lung injury need to take into account both hyperoxia and hypoxemia and that these new models combining both clinical features in preterm infants better reflect the pathogenesis of BPD.…”

Section: Oxygen Requirements Of the Preterm Infantmentioning

confidence: 99%

Oxygen Toxicity to the Immature Lung—Part II: The Unmet Clinical Need for Causal Therapy

Behnke

Dippel

Choi

et al. 2021

IJMS

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Oxygen toxicity continues to be one of the inevitable injuries to the immature lung. Reactive oxygen species (ROS) production is the initial step leading to lung injury and, subsequently, the development of bronchopulmonary dysplasia (BPD). Today, BPD remains the most important disease burden following preterm delivery and results in life-long restrictions in lung function and further important health sequelae. Despite the tremendous progress in the pathomechanistic understanding derived from preclinical models, the clinical needs for preventive or curative therapies remain unmet. This review summarizes the clinical progress on guiding oxygen delivery to the preterm infant and elaborates future directions of research that need to take into account both hyperoxia and hypoxia as ROS sources and BPD drivers. Many strategies have been tested within clinical trials based on the mechanistic understanding of ROS actions, but most have failed to prove efficacy. The majority of these studies were tested in an era before the latest modes of non-invasive respiratory support and surfactant application were introduced or were not appropriately powered. A comprehensive re-evaluation of enzymatic, antioxidant, and anti-inflammatory therapies to prevent ROS injury is therefore indispensable. Strategies will only succeed if they are applied in a timely and vigorous manner and with the appropriate outcome measures.

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“…It should be noted that hyperoxia with intermittent hypoxia affected the number and extent of gene regulations in an unfavorable direction [6,7]. In one study in rats, only the combination of hyperoxia with hypoxemic episodes decreased the antioxidative defense mechanisms, as well as HIF-1α and its downstream activity [8]. These data are not surprising, since hypoxemia leads to the accumulation of purine derivatives such as hypoxanthine during hypoxia-reoxygenation injury.…”

Section: Introductionmentioning

confidence: 98%

Oxygen Toxicity to the Immature Lung—Part I: Pathomechanistic Understanding and Preclinical Perspectives

Choi

Rekers

Dong

et al. 2021

IJMS

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In utero, the fetus and its lungs develop in a hypoxic environment, where HIF-1α and VEGFA signaling constitute major determinants of further development. Disruption of this homeostasis after preterm delivery and extrauterine exposure to high fractions of oxygen are among the key events leading to bronchopulmonary dysplasia (BPD). Reactive oxygen species (ROS) production constitutes the initial driver of pulmonary inflammation and cell death, altered gene expression, and vasoconstriction, leading to the distortion of further lung development. From preclinical studies mainly performed on rodents over the past two decades, the deleterious effects of oxygen toxicity and the injurious insults and downstream cascades arising from ROS production are well recognized. This article provides a concise overview of disease drivers and different therapeutic approaches that have been successfully tested within experimental models. Despite current studies, clinical researchers are still faced with an unmet clinical need, and many of these strategies have not proven to be equally effective in clinical trials. In light of this challenge, adapting experimental models to the complexity of the clinical situation and pursuing new directions constitute appropriate actions to overcome this dilemma. Our review intends to stimulate research activities towards the understanding of an important issue of immature lung injury.

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Effect of intermittent hypoxia or hyperoxia on lung development in preterm rat neonates during constant oxygen therapy

Cited by 12 publications

References 29 publications

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia

Oxygen Toxicity to the Immature Lung—Part II: The Unmet Clinical Need for Causal Therapy

Oxygen Toxicity to the Immature Lung—Part I: Pathomechanistic Understanding and Preclinical Perspectives

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