ArticleThe Journal of biological chemistry2008
Mathematical model of nucleotide regulation on airway epithelia. Implications for airway homeostasis.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Physiology and pathophysiology of human airway mucus.Physiological reviews · 2022Review
- Calcium Signaling in the Photodamaged Skin: In Vivo Experiments and Mathematical Modeling.Function (Oxford, England) · 2022Article
- Purinergic receptors in airway hydration.Biochemical pharmacology · 2021Review
- The therapeutic potential of inorganic polyphosphate: A versatile physiological polymer to control coronavirus disease (COVID-19).Theranostics · 2021Review
- A physiologically-motivated model of cystic fibrosis liquid and solute transport dynamics across primary human nasal epithelia.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- An integrated mathematical epithelial cell model for airway surface liquid regulation by mechanical forces.Journal of theoretical biology · 2018Article
- Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.The Journal of physiology · 2017Article
- A metabolomic, geographic, and seasonal analysis of the contribution of pollen-derived adenosine to allergic sensitization.Metabolomics : Official journal of the Metabolomic Society · 2016Article
- UDP-glucose promotes neutrophil recruitment in the lung.Purinergic signalling · 2016Article
- Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion.Bioscience reports · 2014Article
- A mechanochemical model for auto-regulation of lung airway surface layer volume.Journal of theoretical biology · 2013Article
- Coupled nucleotide and mucin hypersecretion from goblet-cell metaplastic human airway epithelium.American journal of respiratory cell and molecular biology · 2011Article
- Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in mice.American journal of physiology. Renal physiology · 2011Article
- Image-based modeling of lung structure and function.Journal of magnetic resonance imaging : JMRI · 2010Review
- Ebselen is a potent non-competitive inhibitor of extracellular nucleoside diphosphokinase.Purinergic signalling · 2010Article
- Human alveolar type II cells secrete and absorb liquid in response to local nucleotide signaling.The Journal of biological chemistry · 2010Article
- Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo.Experimental eye research · 2010Article
- Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides.The Journal of physiology · 2010Article
- Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3.American journal of physiology. Lung cellular and molecular physiology · 2010Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
In the airways, adenine nucleotides support a complex signaling network mediating host defenses. Released by the epithelium into the airway surface liquid (ASL) layer, they regulate mucus clearance through P2 (ATP) receptors, and following surface metabolism through P1 (adenosine; Ado) receptors. The complexity of ASL nucleotide regulation provides an ideal subject for biochemical network modeling. A mathematical model was developed to integrate nucleotide release, the ectoenzymes supporting the dephosphorylation of ATP into Ado, Ado deamination into inosine (Ino), and nucleoside uptake. The model also includes ecto-adenylate kinase activity and feed-forward inhibition of Ado production by ATP and ADP. The parameters were optimized by fitting the model to experimental data for the steady-state and transient concentration profiles generated by adding ATP to polarized primary cultures of human bronchial epithelial (HBE) cells. The model captures major aspects of ATP and Ado regulation, including their >4-fold increase in concentration induced by mechanical stress mimicking normal breathing. The model also confirmed the independence of steady-state nucleotide concentrations on the ASL volume, an important regulator of airway clearance. An interactive approach between simulations and assays revealed that feed-forward inhibition is mediated by selective inhibition of ecto-5'-nucleotidase. Importantly, the model identifies ecto-adenylate kinase as a key regulator of ASL ATP and proposes novel strategies for the treatment of airway diseases characterized by impaired nucleotide-mediated clearance. These new insights into the biochemical processes supporting ASL nucleotide regulation illustrate the potential of this mathematical model for fundamental and clinical research.
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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.