Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology

Thekkeveedu, Renjithkumar Kalikkot; Guamán, Milenka Cuevas; Shivanna, Binoy

doi:10.1016/j.rmed.2017.10.014

Cited by 290 publications

(261 citation statements)

References 131 publications

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“…The main pathologic finding of bronchopulmonary dysplasia (BPD) in the postsurfactant era is an alveolar arrest resulting in alveolar simplification (the development of fewer but larger alveoli with decreased septation) and decreased density of capillary beds [1][2][3][4][5][6] . Recent studies have revealed that impaired angiogenesis may lead to decreased numbers of alveoli; therefore, enhancement of normal angiogenesis could promote alveolarization in preterm infants 1,3,5,[7][8][9][10] .…”

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confidence: 99%

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

Lee

Nam

et al. 2020

Sci Rep

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Altered pulmonary angiogenesis contributes to disrupted alveolarization, which is the main characteristic of bronchopulmonary dysplasia (BPD). Transforming growth factor β (tGfβ) plays an important role during lung vascular development, and recent studies have demonstrated that endoglin is engaged in the modulation of tGfβ downstream signalling. Although there are two different isoforms of endoglin, L-and S-endoglin, little is known about the effect of S-endoglin in developing lungs. We analysed the expression of both L-and S-endoglin in the lung vasculature and its contribution to tGfβ-activin-like kinase (ALK)-Smad signalling with respect to BPD development. Hyperoxia impaired pulmonary angiogenesis accompanied by alveolar simplification in neonatal mouse lungs. S-endoglin, phosphorylated Smad2/3 and connective tissue growth factor levels were significantly increased in hyperoxia-exposed mice, while L-endoglin, phosphor-Smad1/5 and platelet-endothelial cell adhesion molecule-1 levels were significantly decreased. Hyperoxia suppressed the tubular growth of human pulmonary microvascular endothelial cells (ECs), and the selective inhibition of ALK5 signalling restored tubular growth. These results indicate that hyperoxia alters the balance in two isoforms of endoglin towards increased S-endoglin and that S-endoglin attenuates TGFβ-ALK1-Smad1/5 signalling but stimulates tGfβ-ALK5-Smad2/3 signalling in pulmonary ECs, which may lead to impaired pulmonary angiogenesis in developing lungs. open Scientific RepoRtS | (2020) 10:3043 | https://doi.org/10.1038/s41598-020-59928-x www.nature.com/scientificreports www.nature.com/scientificreports/ through enhancement of the TGFβ-ALK1-Smad1/5 pathway, while connective tissue growth factor (CTGF) expression increases through enhancement of the TGFβ-ALK5-Smad2/3 pathway [27][28][29][30][31] .Several independent findings have demonstrated that endoglin is engaged in TGFβ receptor complex formation and the modulation of downstream signalling [32][33][34][35] . The expression of two alternatively spliced isoforms, long (L-) endoglin and short (S-) endoglin, has been demonstrated in human and mouse lung tissues in vivo 33,34,36,37 . L-endoglin is the predominant isoform, and its pre-mRNA can be alternatively spliced by intron retention, producing the less abundant form, S-endoglin 36,37 . Evidence indicates that L-endoglin, the predominant isoform in ECs, promotes EC proliferation via TGFβ-ALK1 signalling, whereas S-endoglin acts as an antagonist of L-endoglin via activation of the TGFβ-ALK5 pathway 32,33,36,37 .To date, most studies published on endoglin have focused on L-endoglin. It has been found that L-endoglin enhances ALK1-Smad1/5 signalling in ECs, leading to proliferation and migration, which are the main characteristics of the activation phase of angiogenesis 15,18,20,22,[38][39][40][41][42][43] . However, a role of S-endoglin during endothelial senescence was recently described 36,37 . The S-endoglin:L-endoglin ratio increases during the senescence of ECs in vitro as well ...

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confidence: 99%

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

Lee

Nam

et al. 2020

Sci Rep

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“…Hyperoxia exposure in newborn rats closely mimics clinical conditions in preterm infants (Choi et al, ; Zhu et al, ). In our hyperoxia‐induced BPD mouse model, histological analysis of lung sections showed significant alveolar simplification and aberrant pulmonary vascularization (Figures b and c), which are the typical histopathological hallmarks of clinical BPD (Coalson, ; Kalikkot Thekkeveedu, Guaman, & Shivanna, ).…”

Section: Discussionmentioning

confidence: 69%

Peptidome analysis of lung tissues from a hyperoxia‐induced bronchopulmonary dysplasia mouse model: Insights into the pathophysiological process of bronchopulmonary dysplasia

Yin

Wang

Zhang

et al. 2018

Journal Cellular Physiology

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The aim of this study was to identify and compare the peptidomic profiles of lung tissues from neonatal mice with and without bronchopulmonary dysplasia (BPD). Hyperoxia was used to establish the BPD mouse model. Lung tissues obtained on postnatal day (PND) 9 were processed for analysis via histological staining and label-free liquid chromatography-mass spectrometry (LC-MS/MS). Histological analysis of the lung sections from the BPD group showed significant alveolar simplification and aberrant pulmonary vascularization. We identified 3,704 total peptides, of which 63 were differentially expressed in the lung tissues from the BPD group compared with those from the control group. Within this subset, 31 peptides were downregulated, and 32 peptides were upregulated. Bioinformatics analysis suggested several potential roles of the differentially expressed peptides in the pathophysiological process of BPD. In summary, this study highlights novel peptide candidates, and provides new insights for further understanding the molecular mechanism of BPD development.

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“…Prolonged oligohydramnios may be associated with neonatal pulmonary hypoplasia (16,20). It has been pointed out that various factors, including premature lungs, oxygen toxicity and in ammatory mediators, are also involved (21).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Neonatal Bronchopulmonary Dysplasia in Extremely Preterm Premature Rupture of Membranes: A Retrospective Study

Nakamura¹,

Matsunaga²,

Ono³

et al. 2020

Preprint

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Background: Determination of the optimal timing for termination of pregnancy in cases of preterm premature rupture of membranes (pPROM) during the extremely preterm period is still difficult. Bronchopulmonary dysplasia (BPD) is a major disease widely taken into account when determining the prognosis of respiratory disorders in a neonate. Many aspects of this disease remain unclear. With the aim of further improving the prognosis of neonates born to mothers with pPROM, this study examined cases who were diagnosed with pPROM before 28 weeks of gestation. The study analysed risk factors for neonatal BPD and the optimal timing for termination of pregnancy in pPROM cases.Methods:Subjects were 73 cases of singleton pregnancy who were diagnosed with pPROM during the period from 22 weeks and 0 days to 27 weeks and 6 days of gestation. The following factors were retrospectively examined: the gestational week at which a diagnosis of pPROM was made; the gestational week at which delivery occurred; the period for which the volume of amniotic fluid was maintained; and neonatal BPD as a complication. A receiver operating characteristic (ROC) curve was drawn in order to analyse the relationship between the duration of oligohydramnios and the onset of BPD.Results: The mean gestational week at which a diagnosis of amniorrhexis was made was 24.5±1.9 weeks (mean±SD), and that at which delivery occurred was 27.0±3.0 weeks. Fifty-seven cases (78.1%) were diagnosed with oligohydramnios, the mean duration of which was 17.4±20.5 days. The mean birth weight of neonates was 1000±455 g, of which 49 (67.1%) were diagnosed with BPD following birth. No neonates died in this study. Multivariate analysis of various risk factors for the onset of BPD indicated that oligohydramnios is an independent risk factor for BPD. The ROC curve indicated that the cut-off value was 4 days. In this case, the levels of sensitivity and specificity for predicting the onset of neonatal BPD were 0.941 and 0.917 respectively.Conclusion: Our findings suggest that oligohydramnios is an independent risk factor for BPD in cases who are diagnosed with pPROM before 28 weeks of gestation.

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Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology

Cited by 290 publications

References 131 publications

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

Peptidome analysis of lung tissues from a hyperoxia‐induced bronchopulmonary dysplasia mouse model: Insights into the pathophysiological process of bronchopulmonary dysplasia

Risk Factors for Neonatal Bronchopulmonary Dysplasia in Extremely Preterm Premature Rupture of Membranes: A Retrospective Study

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