ArticleThe Journal of clinical investigation2012
Integrin α9β1 in airway smooth muscle suppresses exaggerated airway narrowing.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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
36 citing papers in PubMed, 46 citations in OpenAlex.
- Inflammatory and repair pathways induced in human bronchoalveolar lavage cells with ozone inhalation.PloS one · 2015Trial
- Gut microbiota-activated PLCγ2 monocytes drive atrial fibrillation.Nature communications · 2026Article
- AOC1 regulates labor initiation through spermidine-induced autophagy of placental trophoblast cells via EIF5A hypusination.Nature communications · 2026Article
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- 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
- 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
- Membrane adhesion junctions regulate airway smooth muscle phenotype and function.Physiological reviews · 2023Review
- The integrin ligand SVEP1 regulates GPCR-mediated vasoconstriction via integrins α9β1 and α4β1.British journal of pharmacology · 2022Article
- Transcription of the Envelope Protein by 1-L Protein-RNA Recognition Code Leads to Genes/Proteins That Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis.Current issues in molecular biology · 2022Article
- Pathobiology of Airway Remodeling in Asthma: The Emerging Role of Integrins.Journal of asthma and allergy · 2022Review
- Integrin α2β1 regulates collagen I tethering to modulate hyperresponsiveness in reactive airway disease models.The Journal of clinical investigation · 2021Article
- SVEP1 is a human coronary artery disease locus that promotes atherosclerosis.Science translational medicine · 2021Article
- Preserving Airway Smooth Muscle Contraction in Precision-Cut Lung Slices.Scientific reports · 2020Article
- Reduction in polyamine catabolism leads to spermine-mediated airway epithelial injury and induces asthma features.Allergy · 2018Article
- Molecular Tension Probes to Investigate the Mechanopharmacology of Single Cells: A Step toward Personalized Mechanomedicine.Advanced healthcare materials · 2018Article
- Role of Polyamines in Asthma Pathophysiology.Medical sciences (Basel, Switzerland) · 2018Review
- Fra-2 negatively regulates postnatal alveolar septation by modulating myofibroblast function.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.Mucosal immunology · 2017Article
- Targeting integrin α5β1 ameliorates severe airway hyperresponsiveness in experimental asthma.The Journal of clinical investigation · 2017Article
- α-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFβ activation or collagen production across multiple models of organ fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2016Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α9β1 on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking integrin α9β1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α9β1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α9β1 or treated with integrin α9β1-blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α9β1. Therefore, integrin α9β1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for 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.