ArticleJCI insight2020
Aberrant cell migration contributes to defective airway epithelial repair in childhood wheeze.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Proteasome-dependent cytoskeleton disruption during Leptospira interrogans infection induces aberrant collective cell migration.PLoS pathogens · 2026Article
- Reticular Basement Membrane Remodelling Regulates Bronchial Epithelial Attachment, Barrier Integrity and Inflammatory Signalling in Asthma.Advances in respiratory medicine · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Conservation of gene expression patterns between the amniotic and nasal epithelium at birth.ERJ open research · 2025Article
- Programming of the respiratory epitheliummedRxiv : the preprint server for health sciences · 2025Article
- Innate epithelial and functional differences in airway epithelium of children with acute wheeze.Frontiers in cell and developmental biology · 2025Article
- Airway epithelium respiratory illnesses and allergy (AERIAL) birth cohort: study protocol.Frontiers in allergy · 2024Article
- Transcriptomic analysis of primary nasal epithelial cells reveals altered interferon signalling in preterm birth survivors at one year of age.Frontiers in cell and developmental biology · 2024Article
- Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway inflammation.Redox biology · 2023Article
- Inflammatory related plasma proteins involved in acute preschool wheeze.Clinical and translational allergy · 2023Article
- N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling.BMC molecular and cell biology · 2023Article
- Network analyses of upper and lower airway transcriptomes identify shared mechanisms among children with recurrent wheezing and school-age asthma.Frontiers in immunology · 2023Article
- Viral Infection and Airway Epithelial Immunity in Asthma.International journal of molecular sciences · 2022Review
- AI-Driven Cell Tracking to Enable High-Throughput Drug Screening Targeting Airway Epithelial Repair for Children with Asthma.Journal of personalized medicine · 2022Article
- Real-time imaging of asthmatic epithelial cells identifies migratory deficiencies under type-2 conditions.The Journal of allergy and clinical immunology · 2022Article
- Dysregulated Notch Signaling in the Airway Epithelium of Children with Wheeze.Journal of personalized medicine · 2021Article
- Endotype of allergic asthma with airway obstruction in urban children.The Journal of allergy and clinical immunology · 2021Article
- MiRNA-21 Regulates Bronchial Epithelial Cell Proliferation by Activating Tgfβ1/Smad Signaling Pathway and Its Correlation with Asthma Severity in Children.Iranian journal of public health · 2021Article
- Nasal airway epithelial repair after very preterm birth.ERJ open research · 2021Article
- IGF1R controls mechanosignaling in myofibroblasts required for pulmonary alveologenesis.JCI insight · 2021Article
Corrections and comments
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Authors and funding
26 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal wound repair has been observed in the airway epithelium of patients with chronic respiratory diseases, including asthma. Therapies focusing on repairing vulnerable airways, particularly in early life, present a potentially novel treatment strategy. We report defective lower airway epithelial cell repair to strongly associate with common pre-school-aged and school-aged wheezing phenotypes, characterized by aberrant migration patterns and reduced integrin α5β1 expression. Next generation sequencing identified the PI3K/Akt pathway as the top upstream transcriptional regulator of integrin α5β1, where Akt activation enhanced repair and integrin α5β1 expression in primary cultures from children with wheeze. Conversely, inhibition of PI3K/Akt signaling in primary cultures from children without wheeze reduced α5β1 expression and attenuated repair. Importantly, the FDA-approved drug celecoxib - and its non-COX2-inhibiting analogue, dimethyl-celecoxib - stimulated the PI3K/Akt-integrin α5β1 axis and restored airway epithelial repair in cells from children with wheeze. When compared with published clinical data sets, the identified transcriptomic signature was also associated with viral-induced wheeze exacerbations highlighting the clinical potential of such therapy. Collectively, these results identify airway epithelial restitution via targeting the PI3K-integrin α5β1 axis as a potentially novel therapeutic avenue for childhood wheeze and asthma. We propose that the next step in the therapeutic development process should be a proof-of-concept clinical trial, since relevant animal models to test the crucial underlying premise are unavailable.
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