ArticleProceedings of the National Academy of Sciences of the United States of America2017
Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Cough hypersensitivity risk increases during heatwaves and can be reduced by inhalation of alkaline aerosols of endogenous ions.Scientific reports · 2026Article
- Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator correctors VX-445 and VX-121.The Journal of clinical investigation · 2024Article
- Pseudomonas aeruginosa senses and responds to epithelial potassium flux via Kdp operon to promote biofilm.PLoS pathogens · 2024Article
- Review
- Physiology and pathophysiology of human airway mucus.Physiological reviews · 2022Review
- Purinoreceptors and ectonucleotidases control ATP-induced calcium waveforms and calcium-dependent responses in microglia: Roles of P2 receptors and CD39 in ATP-stimulated microglia.Frontiers in physiology · 2022Article
- A model-informed approach to assess the risk of immune checkpoint inhibitor-induced autoimmune myocarditis.Frontiers in pharmacology · 2022Review
- Hyperinflammation and airway surface liquid dehydration in cystic fibrosis: purinergic system as therapeutic target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Calcium Dynamics and Water Transport in Salivary Acinar Cells.Bulletin of mathematical biology · 2021Review
- ENaC regulation by phospholipids and DGK explained through mathematical modeling.Scientific reports · 2020Article
- Co-localization and confinement of ecto-nucleotidases modulate extracellular adenosine nucleotide distributions.PLoS computational biology · 2020Article
- Article
- A physiologically-motivated model of cystic fibrosis liquid and solute transport dynamics across primary human nasal epithelia.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Thickness of the airway surface liquid layer in the lung is affected in cystic fibrosis by compromised synergistic regulation of the ENaC ion channel.Journal of the Royal Society, Interface · 2019Article
- Simulation of P2X-mediated calcium signalling in microglia.The Journal of physiology · 2019Article
- TheThe European respiratory journal · 2018Article
- Osmolytes and ion transport modulators: new strategies for airway surface rehydration.Current opinion in pharmacology · 2010Review
- Mathematical models of cystic fibrosis as a systemic disease.WIREs mechanisms of diseaseReview
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease. A systems-level description of airway surface liquid (ASL) homeostasis could accelerate development of such therapies. Accordingly, we developed a mathematical model to describe the dynamic coupling of ion and water transport to extracellular purinergic signaling. We trained our model from steady-state and time-dependent experimental measurements made using normal and cystic fibrosis (CF) cultured human airway epithelium. To reproduce CF conditions, reduced chloride secretion, increased potassium secretion, and increased sodium absorption were required. The model accurately predicted ASL height under basal normal and CF conditions and the collapse of surface hydration due to the accelerated nucleotide metabolism associated with CF exacerbations. Finally, the model predicted a therapeutic strategy to deliver nucleotide receptor agonists to effectively rehydrate the ASL of CF airways.
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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.