scholarly journals Effects of Hyperoxia on Mitochondrial Homeostasis: Are Mitochondria the Hub for Bronchopulmonary Dysplasia?

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu Xuefei ◽  
Zhao Xinyi ◽  
Cai Qing ◽  
Zhang Dan ◽  
Liu Ziyun ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Redox Reactions ◽  
Rodent Models ◽  
Cell Plasticity ◽  
Mitochondrial Homeostasis ◽  
Alveolar Development ◽  
Lung Structure ◽  
Neonatal Lung ◽  
High Concentrations

Mitochondria are involved in energy metabolism and redox reactions in the cell. Emerging data indicate that mitochondria play an essential role in physiological and pathological processes of neonatal lung development. Mitochondrial damage due to exposure to high concentrations of oxygen is an indeed important factor for simplification of lung structure and development of bronchopulmonary dysplasia (BPD), as reported in humans and rodent models. Here, we comprehensively review research that have determined the effects of oxygen environment on alveolar development and morphology, summarize changes in mitochondria under high oxygen concentrations, and discuss several mitochondrial mechanisms that may affect cell plasticity and their effects on BPD. Thus, the pathophysiological effects of mitochondria may provide insights into targeted mitochondrial and BPD therapy.

scholarly journals Overexpression of Spock2 in mice leads to altered lung alveolar development and worsens lesions induced by hyperoxia

2020 ◽  
Vol 319 (1) ◽  
pp. L71-L81 ◽  
Author(s):  
Alice Hadchouel ◽  
Marie-Laure Franco-Montoya ◽  
Sophie Guerin ◽  
Marcio Do Cruzeiro ◽  
Mickaël Lhuillier ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Transgenic Mouse Model ◽  
Matrix Metalloproteinase 2 ◽  
Preterm Neonates ◽  
Alveolar Cells ◽  
Very Preterm ◽  
Rat Pups ◽  
Alveolar Development

SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 ( SPOCK2) was previously associated with genetic susceptibility to bronchopulmonary dysplasia in a French population of very preterm neonates. Its expression increases during lung development and is increased after exposure of rat pups to hyperoxia compared with controls bred in room air. To further investigate the role of SPOCK2 during lung development, we designed two mouse models, one that uses a specific anti-Spock2 antibody and one that reproduces the hyperoxia-induced Spock2 expression with a transgenic mouse model resulting in a conditional and lung-targeted overexpression of Spock2. When mice were bred under hyperoxic conditions, treatment with anti-Spock2 antibodies significantly improved alveolarization. Lung overexpression of Spock2 altered alveolar development in pups bred in room air and worsened hyperoxia-induced lesions. Neither treatment with anti-Spock2 antibody nor overexpression of Spock2 was associated with abnormal activation of matrix metalloproteinase-2. These two models did not alter the expression of known players in alveolar development. This study brings strong arguments for the deleterious role of SPOCK2 on lung alveolar development especially after lung injury, suggesting its role in bronchopulmonary dysplasia susceptibility. These effects are not mediated by a deregulation in metalloproteases activity and in expression of factors essential to normal alveolarization. The balance between types 1 and 2 epithelial alveolar cells may be involved.

scholarly journals Animal models of bronchopulmonary dysplasia. The term mouse models

2014 ◽  
Vol 307 (12) ◽  
pp. L936-L947 ◽  
Author(s):  
Jessica Berger ◽  
Vineet Bhandari
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Mouse Models ◽  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Invasive Mechanical Ventilation ◽  
Therapeutic Interventions ◽  
Contributing Factors ◽  
Short Term ◽  
Injury Models

The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.

Mechanisms of Lung Injury and Bronchopulmonary Dysplasia

2016 ◽  
Vol 33 (11) ◽  
pp. 1076-1078 ◽  
Author(s):  
Alan Jobe
Keyword(s):  
Birth Weight ◽  
Lung Injury ◽  
Bronchopulmonary Dysplasia ◽  
Gestational Age ◽  
Lung Development ◽  
Complex Disease ◽  
Extremely Low Birth Weight ◽  
Tobacco Exposure ◽  
Good Definition ◽  
Injury And Repair

Although bronchopulmonary dysplasia (BPD) is the most frequent adverse outcome for infants born at < 30 weeks gestational age, there remain major gaps in understanding the pathophysiology, and thus there are few effective targeted therapies to prevent and treat BPD. This review will focus on the substantial problems and knowledge gaps for the clinician and investigator when considering lung injury and BPD. The epidemiology of BPD is clear: BPD is a lung injury syndrome predominantly in extremely low-birth-weight infants with an incidence that increases as gestation/birth weight decrease, with growth restriction, in males and with fetal exposures and with injury from postdelivery respiratory care. However, we do not have a good definition of BPD that identifies the infants that die of respiratory disease before 36 weeks or that predicts long-term outcomes as well. The injury resulting in BPD likely begins as altered lung development before delivery in many infants (small for gestational age, chorioamnionitis, tobacco exposure), can be initiated by resuscitating at birth, and then amplified by postnatal exposures (oxygen, mechanical ventilation, infection). Conceptually the events leading to BPD are the continued interplay of lung development that is altered progressively by injury and repair to result in poorly defined phenotypes of BPD. The injury pathways prominently cause inflammation, and as a proof of principle, corticosteroids can decrease the incidence and severity of BPD, as demonstrated by three recent trials of the early use of steroids. There are likely “adaptation” and “tolerance” responses that modulate the injury and repair to increase or decrease the damage, interactions that are not understood. BPD is a more complex disease.

Altered lung development in bronchopulmonary dysplasia

2014 ◽  
Vol 100 (3) ◽  
pp. 158-167 ◽  
Author(s):  
Alice Hadchouel ◽  
Marie-Laure Franco-Montoya ◽  
Christophe Delacourt
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Lung Development

scholarly journals Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs

2017 ◽  
Vol 123 (5) ◽  
pp. 1195-1203 ◽  
Author(s):  
Graeme R. Polglase ◽  
Jade Barbuto ◽  
Beth J. Allison ◽  
Tamara Yawno ◽  
Amy E. Sutherland ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Lung Development ◽  
Fetal Lung ◽  
Growth Restriction ◽  
Fetal Sheep ◽  
Respiratory Dysfunction ◽  
Melatonin Administration ◽  
Lung Structure

Oxidative stress arising from suboptimal placental function contributes to a multitude of pathologies in infants compromised by fetal growth restriction (FGR). FGR infants are at high risk for respiratory dysfunction after birth and poor long-term lung function. Our objective was to investigate the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. Placental insufficiency and FGR was surgically induced in 13 fetal sheep at ∼105 days of gestation by ligation of a single umbilical artery. Maternal intravenous melatonin infusion was commenced in seven of the ewes 4 h after surgery and continued until birth. Lambs delivered normally at term and lungs were collected 24 h after birth for histological assessment of lung structure and injury and compared with appropriately grown control lambs ( n = 8). FGR fetuses were hypoxic and had lower glucose during gestation compared with controls. Melatonin administration prevented chronic hypoxia. Within the lung, FGR caused reduced secondary septal crest density and altered elastin deposition compared with controls. Melatonin administration had no effect on the changes to lung structure induced by FGR. We conclude that chronic FGR disrupts septation of the developing alveoli, which is not altered by melatonin administration. These findings suggest that oxidative stress is not the mechanism driving altered lung structure in FGR neonates. Melatonin administration did not prevent disrupted airway development but also had no apparent adverse effects on fetal lung development. NEW & NOTEWORTHY Fetal growth restriction (FGR) results in poor respiratory outcomes, which may be caused by oxidation in utero. We investigated the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. FGR disrupted septation of the developing alveoli, which is not altered by melatonin administration. Oxidative stress may not be the mechanism driving altered lung structure in FGR neonates.

scholarly journals Tenascin-C inactivation impacts lung structure and function beyond lung development

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sandrine Gremlich ◽  
Matthias Roth-Kleiner ◽  
Lucile Equey ◽  
Kleanthis Fytianos ◽  
Johannes C. Schittny ◽  
...  
Keyword(s):  
Lung Development ◽  
Structure And Function ◽  
Tenascin C ◽  
Lung Structure ◽  
And Function
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