Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

Lim, Rebecca; Muljadi, Ruth; Koulaeva, Eugenia; Vosdoganes, Patricia; Chan, Sze Wah Samuel; Acharya, Rutu; Gurusinghe, Seshini; Ritvos, Olli; Pasternack, Arja; Wallace, Euan M.

doi:10.1038/pr.2015.46

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…The top differentially regulated gene in the hyperoxic aCap cells was Inhba ( Fig. 5e; Supplementary Data 10), a member of the TGFβ superfamily suggested to contribute to the pathology of BPD 49 . To validate this finding, we further showed the expression of Inhba/INHBA in Pecam/PECAM positive endothelial cells in both hyperoxic mouse and human BPD lung tissues and in healthy controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage

et al. 2021

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During late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such as development. Here, we use MULTI-seq to generate scRNA-seq profiles of over 66,000 cells from 36 mice during normal or impaired lung development secondary to hyperoxia with validation of some of the findings in lungs from BPD patients. We observe dynamic populations of cells, including several rare cell types and putative progenitors. Hyperoxia exposure, which mimics the BPD phenotype, alters the composition of all cellular compartments, particularly alveolar epithelium, stromal fibroblasts, capillary endothelium and macrophage populations. Pathway analysis and predicted dynamic cellular crosstalk suggest inflammatory signaling as the main driver of hyperoxia-induced changes. Our data provides a single-cell view of cellular changes associated with late lung development in health and disease.

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Section: Resultsmentioning

confidence: 99%

Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage

et al. 2021

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“…The causative factors of BPD are life saving interventions including high airway pressures and oxygen tension in the course of mechanical ventilation. The pathogenesis of BPD consist of postnatal suspension of alveolarisation along with noticeable decrease in type I alveolar epithelial cells (AEC1); and reduction in septal crust density (Lim et al, 2015).…”

Section: Bronchopulmonary Dysplasia (Bpd)mentioning

confidence: 99%

Macrophages: Their role, activation and polarization in pulmonary diseases

et al. 2018

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Macrophages, circulating in the blood or concatenated into different organs and tissues constitute the first barrier against any disease. They are foremost controllers of both innate and acquired immunity, healthy tissue homeostasis, vasculogenesis and congenital metabolism. Two hallmarks of macrophages are diversity and plasticity due to which they acquire a wobbling array of phenotypes. These phenotypes are appropriately synchronized responses to a variety of different stimuli from either the tissue microenvironment or - microbes or their products. Based on the phenotype, macrophages are classified into classically activated/(M1) and alternatively activated/(M2) which are further sub-categorized into M2a, M2b, M2c and M2d based upon gene expression profiles. Macrophage phenotype metamorphosis is the regulating factor in initiation, progression, and termination of numerous inflammatory diseases. Several transcriptional factors and other factors controlling gene expression such as miRNAs contribute to the transformation of macrophages at different points in different diseases. Understanding the mechanisms of macrophage polarization and modulation of their phenotypes to adjust to the micro environmental conditions might provide us a great prospective for designing novel therapeutic strategy. In view of the above, this review summarises the activation of macrophages, the factors intricated in activation along with benefaction of macrophage polarization in response to microbial infections, pulmonary toxicity, lung injury and other inflammatory diseases such as chronic obstructive pulmonary dysplasia (COPD), bronchopulmonary dysplasia (BPD), asthma and sepsis, along with the existing efforts to develop therapies targeting this facet of macrophage biology.

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“…Using transgenic mice that overexpress TGF-␤ or mice with genetic ablation of the type II TGF-␤ receptor (Tgfbr2) in the lung epithelium, Sureshbabu and coworkers (323) described a pivotal role for the TGF-␤/Tgfbr2 axis in mediating arrested alveolarization in the background of hyperoxia. To this end, the ability of several pharmacological agents to limit hyperoxia-induced arrest of alveolarization has been attributed to the ability of these agents to blunt hyperoxiainduced TGF-␤ signaling, as was the case with curcumin (305) and nutritional supplementation with docosahexaenoic acid (345) and an activin A receptor type IIB-Fc antagonist (194).…”

Section: Growth Factorsmentioning

confidence: 99%

Recent advances in the mechanisms of lung alveolarization and the pathogenesis of bronchopulmonary dysplasia

Silva

Nardiello

Pozarska

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

127

117

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Alveolarization is the process by which the alveoli, the principal gas exchange units of the lung, are formed. Along with the maturation of the pulmonary vasculature, alveolarization is the objective of late lung development. The terminal airspaces that were formed during early lung development are divided by the process of secondary septation, progressively generating an increasing number of alveoli that are of smaller size, which substantially increases the surface area over which gas exchange can take place. Disturbances to alveolarization occur in bronchopulmonary dysplasia (BPD), which can be complicated by perturbations to the pulmonary vasculature that are associated with the development of pulmonary hypertension. Disturbances to lung development may also occur in persistent pulmonary hypertension of the newborn in term newborn infants, as well as in patients with congenital diaphragmatic hernia. These disturbances can lead to the formation of lungs with fewer and larger alveoli and a dysmorphic pulmonary vasculature. Consequently, affected lungs exhibit a reduced capacity for gas exchange, with important implications for morbidity and mortality in the immediate postnatal period and respiratory health consequences that may persist into adulthood. It is the objective of this Perspectives article to update the reader about recent developments in our understanding of the molecular mechanisms of alveolarization and the pathogenesis of BPD.

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Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

Abstract: This study suggests that activin A signaling may contribute to the pathology of bronchopulmonary dysplasia.

Cited by 14 publications

References 39 publications

Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage

Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage

Macrophages: Their role, activation and polarization in pulmonary diseases

Recent advances in the mechanisms of lung alveolarization and the pathogenesis of bronchopulmonary dysplasia

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