ArticleThe Journal of clinical investigation2021
Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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Who cites it
60 citing papers in PubMed, 87 citations in OpenAlex.
- Targeting Elastin-Derived Peptides Reverses Alveolar Epithelial Dysfunction in Chronic Obstructive Pulmonary Disease.MedComm · 2026Article
- Mesenchyme-derived inflammation during the saccular stage recruits macrophages and alters lung development.JCI insight · 2026Article
- Association between the Dietary Inflammatory Index and lung function in exacerbated chronic obstructive pulmonary disease: The mediating role of inflammatory indicators.Asia Pacific journal of clinical nutrition · 2026Article
- Identification of common genetic features and pathways for osteoporosis with frozen shoulder by integrated bioinformatics analysis and machine learning.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Association between a novel nutritional index and coronary heart disease in COPD patients: a retrospective study in China.BMC pulmonary medicine · 2026Article
- A Clinical Cut-Off Value for the Systemic Immune-Inflammation Index to Predict Frequent Exacerbations in Stable COPD.Medicina (Kaunas, Lithuania) · 2026Observational
- Neutrophils as critical orchestrators of chronic inflammation.Cellular & molecular immunology · 2026Review
- Impact of intranasal cigarette smoke exposure on murine peripheral immune responses and lung pathology.Frontiers in toxicology · 2026Article
- Neutrophil Heterogeneity in Airway Inflammatory Diseases.Inflammation · 2025Review
- Defining endotypes of bronchopulmonary dysplasia in preterm infants to improve precision-based therapies.JCI insight · 2025Review
- Atypical mesenchyme in congenital pulmonary airways malformation: a promising new focus.Respiratory research · 2025Article
- Identification of telomere maintenance related biomarkers and regulatory mechanisms in chronic obstructive pulmonary disease by machine learning algorithm.Scientific reports · 2025Article
- Systemic heparin administration impairs lung development in neonatal mice.Scientific reports · 2025Article
- Article
- Correlation of neutrophil percentage-to-albumin ratio with lung function in American adults: a population study.BMC pulmonary medicine · 2025Article
- Association between C-reactive protein to albumin ratio and chronic obstructive pulmonary disease: a cross-sectional study.BMC pulmonary medicine · 2025Article
- Article
- Fyn kinase mediates the development of rats with chronic obstructive pulmonary disease by modulating the activation of p38 MAPK and NF-κB.Iranian journal of basic medical sciences · 2025Article
- Development and validation of a nomogram for predicting bacterial infections in patients with acute exacerbation of chronic obstructive pulmonary disease.Experimental and therapeutic medicine · 2025Article
- Association Between C-Reactive Protein to Lymphocyte Ratio and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.International journal of chronic obstructive pulmonary disease · 2025Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 1 country.
Funding
Abstract
Emerging evidence indicates that early life events can increase the risk for developing chronic obstructive pulmonary disease (COPD). Using an inducible transgenic mouse model for NF-κB activation in the airway epithelium, we found that a brief period of inflammation during the saccular stage (P3-P5) but not alveolar stage (P10-P12) of lung development disrupted elastic fiber assembly, resulting in permanent reduction in lung function and development of a COPD-like lung phenotype that progressed through 24 months of age. Neutrophil depletion prevented disruption of elastic fiber assembly and restored normal lung development. Mechanistic studies uncovered a role for neutrophil elastase (NE) in downregulating expression of critical elastic fiber assembly components, particularly fibulin-5 and elastin. Further, purified human NE and NE-containing exosomes from tracheal aspirates of premature infants with lung inflammation downregulated elastin and fibulin-5 expression by saccular-stage mouse lung fibroblasts. Together, our studies define a critical developmental window for assembling the elastin scaffold in the distal lung, which is required to support lung structure and function throughout the lifespan. Although neutrophils play a well-recognized role in COPD development in adults, neutrophilic inflammation may also contribute to early-life predisposition to COPD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.