ArticleThe Journal of clinical investigation2021
Integrin α2β1 regulates collagen I tethering to modulate hyperresponsiveness in reactive airway disease models.
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 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Structural and cellular mechanisms of mucus plugging in the larger airways.Chinese medical journal pulmonary and critical care medicine · 2026Review
- The emerging role of integrin signaling in pulmonary vascular disease.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Histopathological alterations in airways associated with physiological changes in airway allergy phenotypes.Frontiers in allergy · 2026Article
- Structure-Based Discovery of Potent and Selective Small-Molecule α5β1 Integrin Inhibitors for Asthma Therapy.ACS omega · 2025Article
- Enhanced engraftment and immunomodulatory effects of integrin alpha-2-overexpressing mesenchymal stromal cells in lipopolysaccharide-induced acute lung injury.Stem cell research & therapy · 2025Article
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- Lumican Is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting Vascular Smooth Cells Senescence Through Interacting With Integrin α2β1.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- IL-13 and IL-17A activate β1 integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to enhance force transmission in airway smooth muscle.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The integrin receptor betaRespiratory research · 2024Article
- IL-13 and IL-17A Activate β1 Integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to Enhance Force Transmission in Airway Smooth Muscle.bioRxiv : the preprint server for biology · 2024Article
- Mechanobiology of Type 1 hypersensitivity: Elucidating the impacts of mechanical forces in allergic reactions.Mechanobiology in medicine · 2024Review
- Pathobiology of Airway Remodeling in Asthma: The Emerging Role of Integrins.Journal of asthma and allergy · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Severe asthma remains challenging to manage and has limited treatment options. We have previously shown that targeting smooth muscle integrin α5β1 interaction with fibronectin can mitigate the effects of airway hyperresponsiveness by impairing force transmission. In this study, we show that another member of the integrin superfamily, integrin α2β1, is present in airway smooth muscle and capable of regulating force transmission via cellular tethering to the matrix protein collagen I and, to a lesser degree, laminin-111. The addition of an inhibitor of integrin α2β1 impaired IL-13-enhanced contraction in mouse tracheal rings and human bronchial rings and abrogated the exaggerated bronchoconstriction induced by allergen sensitization and challenge. We confirmed that this effect was not due to alterations in classic intracellular myosin light chain phosphorylation regulating muscle shortening. Although IL-13 did not affect surface expression of α2β1, it did increase α2β1-mediated adhesion and the level of expression of an activation-specific epitope on the β1 subunit. We developed a method to simultaneously quantify airway narrowing and muscle shortening using 2-photon microscopy and demonstrated that inhibition of α2β1 mitigated IL-13-enhanced airway narrowing without altering muscle shortening by impairing the tethering of muscle to the surrounding matrix. Our data identified cell matrix tethering as an attractive therapeutic target to mitigate the severity of airway contraction in asthma.
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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.