ArticlePloS one2012
An RGS4-mediated phenotypic switch of bronchial smooth muscle cells promotes fixed airway obstruction in asthma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- N-cadherin antagonism is bronchoprotective in severe asthma models.Science advances · 2024Article
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms.The Journal of biological chemistry · 2024Article
- C-KitIranian journal of basic medical sciences · 2022Article
- RGS5 Determines Neutrophil Migration in the Acute Inflammatory Phase of Bleomycin-Induced Lung Injury.International journal of molecular sciences · 2021Article
- RGS proteins, GRKs, and beta-arrestins modulate G protein-mediated signaling pathways in asthma.Pharmacology & therapeutics · 2021Review
- RGS4 promotes allergen- and aspirin-associated airway hyperresponsiveness by inhibiting PGE2 biosynthesis.The Journal of allergy and clinical immunology · 2020Article
- BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins.Nature communications · 2020Article
- RGS4 Regulates Proliferation And Apoptosis Of NSCLC Cells Via microRNA-16 And Brain-Derived Neurotrophic Factor.OncoTargets and therapy · 2019Article
- PPARγ Agonist PGZ Attenuates OVA-Induced Airway Inflammation and Airway Remodeling via RGS4 Signaling in Mouse Model.Inflammation · 2018Article
- A bronchoprotective role forAllergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2018Article
- RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice.American journal of respiratory cell and molecular biology · 2018Article
- Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Functional Effects of WNT1-Inducible Signaling Pathway Protein-1 on Bronchial Smooth Muscle Cell Migration and Proliferation in OVA-Induced Airway Remodeling.Inflammation · 2016Article
- Regulator of G-protein signaling 2 repression exacerbates airway hyper-responsiveness and remodeling in asthma.American journal of respiratory cell and molecular biology · 2015Article
- Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells.Allergy · 2014Article
- Loss of regulator of G protein signaling 5 promotes airway hyperresponsiveness in the absence of allergic inflammation.The Journal of allergy and clinical immunology · 2014Article
- Airway smooth muscle in airway reactivity and remodeling: what have we learned?American journal of physiology. Lung cellular and molecular physiology · 2013Review
- Uses of Remnant Human Lung Tissue for Mechanical Stretch Studies.Cellular and molecular bioengineering · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM) mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4) in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR)-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe 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.