ArticleProceedings of the National Academy of Sciences of the United States of America2024
IL-13 and IL-17A activate β1 integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to enhance force transmission in airway smooth muscle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Asthma endotypes and theratypes.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Fasudil improves neutrophilic asthma by influencing M1 macrophage polarization and the expression of the NF-κB/TLR-2/RPS3 pathway.American journal of translational research · 2026Article
- 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
- Tackling Allergic Airway Inflammation with Organic Sheet-Like Nanoplatforms by Targeted Elimination of Epithelial Small Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- High PEEP Activates ITGB1, Inducing Diaphragm Fibrosis During Prolonged Mechanical Ventilation.Biomolecules · 2025Article
- Single-Cell RNA Sequencing Identifies a Unique Macrophage Population in a Mouse Model of Ozone-induced Asthma Exacerbation.American journal of respiratory cell and molecular biology · 2025Article
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- Targeting IL-13 and IL-4 in Asthma: Therapeutic Implications on Airway Remodeling in Severe Asthma.Clinical reviews in allergy & immunology · 2025Review
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- Inflammation and platelet hyperresponsiveness in coronary artery disease and the influence of Talin-1/αIIbβ3-mediated bidirectional signaling pathway.Frontiers in pharmacology · 2025Article
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Abstract
Integrin activation resulting in enhanced adhesion to the extracellular matrix plays a key role in fundamental cellular processes. Although integrin activation has been extensively studied in circulating cells such as leukocytes and platelets, much less is known about the regulation and functional impact of integrin activation in adherent cells such as smooth muscle. Here, we show that two different asthmagenic cytokines, IL-13 and IL-17A, activate type I and IL-17 cytokine receptor families, respectively, to enhance adhesion of airway smooth muscle. These cytokines also induce activation of β1 integrins detected by the conformation-specific antibody HUTS-4. Moreover, HUTS-4 binding is increased in the smooth muscle of patients with asthma compared to nonsmokers without lung disease, suggesting a disease-relevant role for integrin activation in smooth muscle. Indeed, integrin activation induced by the β1-activating antibody TS2/16, the divalent cation manganese, or the synthetic peptide β1-CHAMP that forces an extended-open integrin conformation dramatically enhances force transmission in smooth muscle cells and airway rings even in the absence of cytokines. We demonstrate that cytokine-induced activation of β1 integrins is regulated by a common pathway of NF-κB-mediated induction of RhoA and its effector Rho kinase, which in turn stimulates PIP5K1γ-mediated synthesis of PIP
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