ArticleAmerican journal of respiratory cell and molecular biology2020
Antisense Oligonucleotides Targeting Jagged 1 Reduce House Dust Mite-induced Goblet Cell Metaplasia in the Adult Murine Lung.
Article in American journal of respiratory cell and molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 37 citations in OpenAlex.
- Multifaceted mechanistic exploration ofFrontiers in cell and developmental biology · 2026Article
- The immunology of asthma.Nature immunology · 2025Review
- Article
- Mucins and Their Roles in Asthma.Immunological reviews · 2025Review
- Pulmonary-delivered Anticalin Jagged-1 antagonists reduce experimental airway mucus hyperproduction and obstruction.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Notch Signaling Pathway Interfering as a Possible Asthma Treatment: A Narrative Review.Journal of asthma and allergy · 2025Review
- Emerging cell and molecular targets for treating mucus hypersecretion in asthma.Allergology international : official journal of the Japanese Society of Allergology · 2024Review
- Sphingosine kinase 1-specific inhibitor PF543 reduces goblet cell metaplasia of bronchial epithelium in an acute asthma model.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Airways Type-2 Related Disorders: Multiorgan, Systemic or Syndemic Disease?International journal of molecular sciences · 2024Review
- New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis.Clinical science (London, England : 1979) · 2023Review
- Unlocking the potential of RNA-based therapeutics in the lung: current status and future directions.Frontiers in genetics · 2023Review
- Targeted Inhibition of Select Extracellular Signal-regulated Kinases 1 and 2 Functions Mitigates Pathological Features of Asthma in Mice.American journal of respiratory cell and molecular biology · 2023Article
- The emerging role of NOTCH3 receptor signalling in human lung diseases.Expert reviews in molecular medicine · 2022Review
- Intratracheally administered LNA gapmer antisense oligonucleotides induce robust gene silencing in mouse lung fibroblasts.Nucleic acids research · 2022Article
- Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease.JCI insight · 2022Article
- SARS-CoV-2 Infection and Lung Regeneration.Clinical microbiology reviews · 2022Review
- Human airway organoids as 3DFrontiers in bioengineering and biotechnology · 2022Article
- Midkine-Notch2 Pathway Mediates Excessive Proliferation of Airway Smooth Muscle Cells in Chronic Obstructive Lung Disease.Frontiers in pharmacology · 2022Article
- Dysregulated Notch Signaling in the Airway Epithelium of Children with Wheeze.Journal of personalized medicine · 2021Article
- The diversity of adult lung epithelial stem cells and their niche in homeostasis and regeneration.Science China. Life sciences · 2021Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Goblet cell metaplasia, excessive mucus production, and inadequate mucus clearance accompany and exacerbate multiple chronic respiratory disorders, such as asthma and chronic obstructive pulmonary disease. Notch signaling plays a central role in controlling the fate of multiple cell types in the lung, including goblet cells. In the present study, we explored the therapeutic potential of modulating the Notch pathway in the adult murine lung using chemically modified antisense oligonucleotides (ASOs). To this end, we designed and characterized ASOs targeting the Notch receptors Notch1, Notch2, and Notch3 and the Notch ligands Jag1 (Jagged 1) and Jag2 (Jagged 2). Pulmonary delivery of ASOs in healthy mice or mice exposed to house dust mite, a commonly used mouse model of asthma, resulted in a significant reduction of the respective mRNAs in the lung. Furthermore, ASO-mediated knockdown of Jag1 or Notch2 in the lungs of healthy adult mice led to the downregulation of the club cell marker Scgb1a1 and the concomitant upregulation of the ciliated cell marker FoxJ1 (forkhead box J1). Similarly, ASO-mediated knockdown of Jag1 or Notch2 in the house dust mite disease model led to reduced goblet cell metaplasia and decreased mucus production. Because goblet cell metaplasia and excessive mucus secretion are a common basis for many lung pathologies, we propose that ASO-mediated inhibition of JAG1 could provide a novel therapeutic path for the treatment of multiple chronic respiratory diseases.
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