ArticleThe Journal of biological chemistry2010
Decreased soluble adenylyl cyclase activity in cystic fibrosis is related to defective apical bicarbonate exchange and affects ciliary beat frequency regulation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
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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
37 citing papers in PubMed, 48 citations in OpenAlex.
- Hyaluronan and layilin mediate loss of airway epithelial barrier function induced by cigarette smoke by decreasing E-cadherin.The Journal of biological chemistry · 2012Trial
- Pharmacological regulation of airway ciliary motility: endogenous mediators, pharmaceutical agents, and natural compounds with a focus on ginsenoside Rd.Journal of natural medicines · 2026Review
- Specialized proresolving mediator resolvin E1 corrects the altered cystic fibrosis nasal epithelium cilia beating dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Toward a Systematic Assessment of Sex Differences in Cystic Fibrosis.Journal of personalized medicine · 2023Article
- Transport of Designed Ankyrin Repeat Proteins through reconstituted human bronchial epithelia and protection against SARS-CoV-2.Scientific reports · 2023Article
- Role of Secondary Organic Matter on Soot Particle Toxicity in Reconstituted Human Bronchial Epithelia Exposed at the Air-Liquid Interface.Environmental science & technology · 2022Article
- Responses of reconstituted human bronchial epithelia from normal and health-compromised donors to non-volatile particulate matter emissions from an aircraft turbofan engine.Environmental pollution (Barking, Essex : 1987) · 2022Article
- CFTR Protein: Not Just a Chloride Channel?Cells · 2021Review
- Airway Surface Liquid pH Regulation in Airway Epithelium Current Understandings and Gaps in Knowledge.International journal of molecular sciences · 2021Review
- Mucociliary Respiratory Epithelium Integrity in Molecular Defense and Susceptibility to Pulmonary Viral Infections.Biology · 2021Review
- Hyperglycaemia in cystic fibrosis adversely affects BK channel function critical for mucus clearance.The European respiratory journal · 2021Article
- Glycated Albumin Triggers an Inflammatory Response in the Human Airway Epithelium and Causes an Increase in Ciliary Beat Frequency.Frontiers in physiology · 2021Article
- Losartan reduces cigarette smoke-induced airway inflammation and mucus hypersecretion.ERJ open research · 2021Article
- Pendrin stimulates a chloride absorption pathway to increase CFTR-mediated chloride secretion from Cystic Fibrosis airway epithelia.FASEB bioAdvances · 2020Article
- Airway Resistance Caused by Sphingomyelin Synthase 2 Insufficiency in Response to Cigarette Smoke.American journal of respiratory cell and molecular biology · 2020Article
- TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating.The Journal of pathology · 2019Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- Seeing cilia: imaging modalities for ciliary motion and clinical connections.American journal of physiology. Lung cellular and molecular physiology · 2018Review
- The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology.Mediators of inflammation · 2018Review
- Modulation of Wnt signaling is essential for the differentiation of ciliated epithelial cells in human airways.FEBS letters · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Human airway cilia contain soluble adenylyl cyclase (sAC) that produces cAMP upon HCO(3)(-)/CO(2) stimulation to increase ciliary beat frequency (CBF). Because apical HCO(3)(-) exchange depends on cystic fibrosis transmembrane conductance regulator (CFTR), malfunctioning CFTR might impair sAC-mediated CBF regulation in cells from patients with cystic fibrosis (CF). By Western blot, sAC isoforms are equally expressed in normal and CF airway epithelial cells, but CBF decreased more in CF than normal cells upon increased apical HCO(3)(-)/CO(2) exposure in part because of greater intracellular acidification from unbalanced CO(2) influx (estimated by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) fluorescence). Importantly, ciliated cell-specific cAMP production (estimated by FRET fluorescence ratio changes of tagged cAMP-dependent protein kinase (PKA) subunits expressed under a ciliated cell-specific promoter) in response to increased apical HCO(3)(-)/CO(2) perfusion was higher in normal compared with CF cells. Inhibition of bicarbonate influx via CFTR (CFTR(inh)172) and inhibition of sAC (KH7) and PKA activation (H89) led to larger CBF declines in normal cells, now comparable with changes seen in CF cells. These inhibitors also reduced FRET changes in normal cells to the level of CF cells with the expected exception of H89, which does not prevent dissociation of the fluorescently tagged PKA subunits. Basolateral permeabilization and subsequent perfusion with HCO(3)(-)/CO(2) rescued CBF and FRET changes in CF cells to the level of normal cells. These results suggest that CBF regulation by sAC-produced cAMP could be impaired in CF, thereby possibly contributing to mucociliary dysfunction in this disease, at least during disease exacerbations when airway acidification is common.
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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.