ArticleAmerican journal of respiratory and critical care medicine2016
Cystic Fibrosis Transmembrane Conductance Regulator in Sarcoplasmic Reticulum of Airway Smooth Muscle. Implications for Airway Contractility.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 68 citations in OpenAlex.
- Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Paranasal Sinus CT and Polysomnographic Findings in Adults with Cystic Fibrosis: Implications for Obstructive Sleep Apnea.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Porcine airway tissue explant culture at a hydrogel-air interface to model submucosal glands in cystic fibrosis progression and therapy.Science advances · 2025Article
- CFTR negatively reprograms Th2 cell responses, and CFTR potentiation restrains allergic airway inflammation.JCI insight · 2025Article
- High throughput screening of airway constriction in mouse lung slices.Scientific reports · 2024Article
- Fecal dysbiosis and inflammation in intestinal-specific Cftr knockout mice on regimens preventing intestinal obstruction.Physiological genomics · 2024Article
- Pancreatic enzymes digest obstructive meconium from cystic fibrosis pig intestines.Frontiers in pediatrics · 2024Article
- Investigating the role of CFTR in human and mouse myometrium.Current research in physiology · 2024Article
- CFTR dysfunction in smooth muscle drives TGFβ dependent airway hyperreactivity.Respiratory research · 2023Article
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond.The European respiratory journal · 2023Review
- Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis.Cells · 2021Review
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model.Scientific reports · 2021Article
- Cystic Fibrosis Human Organs-on-a-Chip.Micromachines · 2021Review
- Asthma in Cystic Fibrosis: Definitions and Implications of This Overlap Syndrome.Current allergy and asthma reports · 2021Review
- Research advances in molecular mechanisms underlying the pathogenesis of cystic fibrosis: From technical improvement to clinical applications (Review).Molecular medicine reports · 2020Review
- The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Fibrocyte accumulation in the lungs of cystic fibrosis patients.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Article
- Subacute TGFβ Exposure Drives Airway Hyperresponsiveness in Cystic Fibrosis Mice through the PI3K Pathway.American journal of respiratory cell and molecular biology · 2020Article
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
rationaleAn asthma-like airway phenotype has been described in people with cystic fibrosis (CF). Whether these findings are directly caused by loss of CF transmembrane conductance regulator (CFTR) function or secondary to chronic airway infection and/or inflammation has been difficult to determine.
objectivesAirway contractility is primarily determined by airway smooth muscle. We tested the hypothesis that CFTR is expressed in airway smooth muscle and directly affects airway smooth muscle contractility.
methodsNewborn pigs, both wild type and with CF (before the onset of airway infection and inflammation), were used in this study. High-resolution immunofluorescence was used to identify the subcellular localization of CFTR in airway smooth muscle. Airway smooth muscle function was determined with tissue myography, intracellular calcium measurements, and regulatory myosin light chain phosphorylation status. Precision-cut lung slices were used to investigate the therapeutic potential of CFTR modulation on airway reactivity. MEASUREMENTS AND MAIN
resultsWe found that CFTR localizes to the sarcoplasmic reticulum compartment of airway smooth muscle and regulates airway smooth muscle tone. Loss of CFTR function led to delayed calcium reuptake following cholinergic stimulation and increased myosin light chain phosphorylation. CFTR potentiation with ivacaftor decreased airway reactivity in precision-cut lung slices following cholinergic stimulation.
conclusionsLoss of CFTR alters porcine airway smooth muscle function and may contribute to the airflow obstruction phenotype observed in human CF. Airway smooth muscle CFTR may represent a therapeutic target in CF and other diseases of airway narrowing.
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