ArticleThe American journal of pathology2016
Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Sex-specific modulation of lung function and transcriptome in neonate mice exposed to thirdhand electronic-cigarette aerosols.Pediatric research · 2026Article
- Mesenchyme-derived inflammation during the saccular stage recruits macrophages and alters lung development.JCI insight · 2026Article
- Defining endotypes of bronchopulmonary dysplasia in preterm infants to improve precision-based therapies.JCI insight · 2025Review
- Fetal Tracheal Occlusion Correlates with Normalized YAP Expression and Alveolar Epithelial Differentiation in Congenital Diaphragmatic Hernia.American journal of respiratory cell and molecular biology · 2025Article
- Fetal origin of bronchopulmonary dysplasia: contribution of intrauterine inflammation.Molecular medicine (Cambridge, Mass.) · 2024Review
- Distribution and associations of anterior lens zonules lengths in patients with cataract.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- A Tracheal Aspirate-derived Airway Basal Cell Model Reveals a Proinflammatory Epithelial Defect in Congenital Diaphragmatic Hernia.American journal of respiratory and critical care medicine · 2023Article
- Role of Postnatal Corticosteroids in the Treatment or Prevention of Bronchopulmonary Dysplasia.Sisli Etfal Hastanesi tip bulteni · 2023Review
- Defining the versican interactome in lung health and disease.American journal of physiology. Cell physiology · 2022Review
- Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD".American journal of respiratory cell and molecular biology · 2022Review
- A single-cell atlas of mouse lung development.Development (Cambridge, England) · 2021Article
- Article
- PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD.The Journal of clinical investigation · 2021Article
- Implications for Extracellular Matrix Interactions With Human Lung Basal Stem Cells in Lung Development, Disease, and Airway Modeling.Frontiers in pharmacology · 2021Review
- Prenatal inflammation enhances antenatal corticosteroid-induced fetal lung maturation.JCI insight · 2020Article
- Phenotypes of Bronchopulmonary Dysplasia.International journal of molecular sciences · 2020Review
- Hyperoxia Injury in the Developing Lung Is Mediated by Mesenchymal Expression of Wnt5A.American journal of respiratory and critical care medicine · 2020Article
- β1 Integrin regulates adult lung alveolar epithelial cell inflammation.JCI insight · 2020Article
- Prevention of Oxygen-Induced Inflammatory Lung Injury by Caffeine in Neonatal Rats.Oxidative medicine and cellular longevity · 2020Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase β transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality. Epithelial-derived inflammation resulted in disrupted elastic fiber organization and down-regulation of elastin assembly components, including fibulins 4 and 5, lysyl oxidase like-1, and fibrillin-1. Fibulin-5 expression by saccular stage lung fibroblasts was consistently inhibited by treatment with bronchoalveolar lavage fluid from inhibitory κB kinase β transactivated mice, Escherichia coli lipopolysaccharide, or tracheal aspirates from preterm infants exposed to chorioamnionitis. Expression of a dominant NF-κB inhibitor in fibroblasts restored fibulin-5 expression after lipopolysaccharide treatment, whereas reconstitution of fibulin-5 rescued extracellular elastin assembly by saccular stage lung fibroblasts. Elastin organization was disrupted in saccular stage lungs of preterm infants exposed to systemic inflammation. Our study reveals a critical window for elastin assembly during the saccular stage that is disrupted by inflammatory signaling and could be amenable to interventions that restore elastic fiber assembly in the developing lung.
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