ArticleThe Journal of clinical investigation2017
Targeting integrin α5β1 ameliorates severe airway hyperresponsiveness in experimental asthma.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 33 citations in OpenAlex.
- Shared ligand-blocking mechanism but distinct conformational modulation by α5-targeting antibodies BIIG2 and MINT1526A.Structure (London, England : 1993) · 2026Article
- The emerging role of integrin signaling in pulmonary vascular disease.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- The Role of Aryl Hydrocarbon Receptor in Airway Remodeling: Mechanistic Insights Across Cellular Functions.Clinical reviews in allergy & immunology · 2026Review
- The importance of mechanical forces in chronic respiratory diseases.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Structure-Based Discovery of Potent and Selective Small-Molecule α5β1 Integrin Inhibitors for Asthma Therapy.ACS omega · 2025Article
- Shared ligand-blocking mechanism but distinct conformational modulation by α5-targeting antibodies BIIG2 and MINT1526A.bioRxiv : the preprint server for biology · 2025Article
- Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.Circulation · 2025Article
- 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
- Polarized focal adhesion kinase activity within a focal adhesion during cell migration.Nature chemical biology · 2023Article
- Pathobiology of Airway Remodeling in Asthma: The Emerging Role of Integrins.Journal of asthma and allergy · 2022Review
- In Vivo protection from SARS-CoV-2 infection by ATN-161 in k18-hACE2 transgenic mice.Life sciences · 2021Article
- Integrin α2β1 regulates collagen I tethering to modulate hyperresponsiveness in reactive airway disease models.The Journal of clinical investigation · 2021Article
- RGD-binding integrins and TGF-β in SARS-CoV-2 infections - novel targets to treat COVID-19 patients?Clinical & translational immunology · 2021Review
- Mast Cell Chymase and Kidney Disease.International journal of molecular sciences · 2020Review
- Dual antagonists of α5β1/αvβ1 integrin for airway hyperresponsiveness.Bioorganic & medicinal chemistry letters · 2020Article
- Anti-Inflammatory Effects of aMolecules (Basel, Switzerland) · 2020Article
- Angiopoietin-like 2 upregulation promotes human chondrocyte injury via NF-κB and p38/MAPK signaling pathway.Journal of bone and mineral metabolism · 2019Article
- Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth.iScience · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no further effect from chymase. We identified α5β1 as the primary fibronectin-binding integrin in ASM, and α5β1-specific blockade inhibited focal adhesion phosphorylation and IL-13-enhanced contraction, with no additional effect from chymase. Delivery of an α5β1 inhibitor into murine airways abrogated the exaggerated bronchoconstriction induced by allergen sensitization and challenge. Finally, α5β1 blockade enhanced the effect of the bronchodilator isoproterenol on airway relaxation. Our data identify the α5β1 integrin as a potential 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.