ArticleAllergy2017
Beyond epithelial-to-mesenchymal transition: Common suppression of differentiation programs underlies epithelial barrier dysfunction in mild, moderate, and severe asthma.
Article in Allergy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- Increased potential for atherogenic changes in asthma: evidence from transcriptomic studies of arterial endothelial cells.Respiratory research · 2026Article
- FABP4-mediated lipid droplet accumulation drives epithelial-mesenchymal transition and aggravates alveolar epithelial barrier disruption.Clinical and translational medicine · 2026Article
- Single-cell profiling demonstrates the combined effect of wheeze phenotype and infant viral infection on airway epithelial development.Science advances · 2025Article
- Review
- Risk factors for bronchiolitis obliterans development in children after Mycoplasma pneumoniae pneumonia: a retrospective study of 981 patients.Italian journal of pediatrics · 2025Article
- The Non-Antibacterial Effects of Azithromycin and Other Macrolides on the Bronchial Epithelial Barrier and Cellular Differentiation.International journal of molecular sciences · 2025Article
- New insights into mesenchymal stem cells in inflammatory subtypes of asthma.Frontiers in immunology · 2025Review
- Increased allergic inflammation and decreased lung insulin sensitivity in offspring of obese allergic mothers.Journal of leukocyte biology · 2024Article
- Multifaceted roles of mitochondria in asthma.Cell biology and toxicology · 2024Review
- Article
- DNA methylation-mediatedFrontiers in molecular biosciences · 2024Article
- How early life respiratory viral infections impact airway epithelial development and may lead to asthma.Frontiers in pediatrics · 2024Review
- Epithelial-Mesenchymal Transition Mechanisms in Chronic Airway Diseases: A Common Process to Target?International journal of molecular sciences · 2023Review
- Diet-induced obesity worsens allergen-induced type 2/type 17 inflammation in airways by enhancing DUOX1 activation.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression.Canadian respiratory journal · 2023Review
- Multi-omics analyses of glucose metabolic reprogramming in colorectal cancer.Frontiers in immunology · 2023Article
- MicroRNA-21 promotes epithelial-mesenchymal transition and migration of human bronchial epithelial cells by targeting poly (ADP-ribose) polymerase-1 and activating PI3K/AKT signaling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Sigma-1 Receptor Alleviates Airway Inflammation and Airway Remodeling Through AMPK/CXCR4 Signal Pathway.Inflammation · 2022Article
- Cellular and systemic energy metabolic dysregulation in asthma development-a hypothesis-generating approach.The Journal of allergy and clinical immunology · 2022Article
- Asthma and Post-Asthmatic Fibrosis: A Search for New Promising Molecular Markers of Transition from Acute Inflammation to Pulmonary Fibrosis.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEpithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood.
methodsWe used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes. We objectively confirmed these findings in epithelial brushings and primary asthmatic epithelial cells cultured in different biological contexts.
resultsWe found a striking suppression of epithelial differentiation in asthma, overrepresented by insufficiency in insulin and Notch signaling, but with the absence of conventional EMT markers. We identified EFNB2, FGFR1, FGFR2, INSR, IRS2, NOTCH2, TLE1, and NTRK2 as novel markers central to dysregulation of epithelial-mesenchymal signaling, but surprisingly overlooked in asthma research. We found that this "core" signature of asthma is shared by mild, moderate, and severe forms of disease, progressing with severity. Loss of epithelial differentiation induced by insulin deprivation in normal human bronchial epithelial cells cultured in organotypic conditions closely approximated gene expression in asthmatic epithelial brushings.
conclusionsThe comparative analysis of publically available transcriptomes demonstrated that epithelial barrier dysfunction in asthma is characterized by persistent underlying de-differentiation program with complex etiology. The lasting alteration of the asthmatic epithelial cell transcriptome implicates regulation involving metabolism and epigenetics, beyond EMT driven by injury and repair in chronic inflammation.
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