Evidence map›Paper›PMID 20042712›Full record

ArticleAmerican journal of respiratory cell and molecular biology2010

Activation of the cystic fibrosis transmembrane conductance regulator by the flavonoid quercetin: potential use as a biomarker of ΔF508 cystic fibrosis transmembrane conductance regulator rescue.

Louise C Pyle, Jennifer C Fulton, Peter A Sloane, Kyle Backer, Marina Mazur, Jeevan Prasain, Stephen Barnes, J P Clancy, Steven M Rowe

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Citrus Flavonoids for Cystic Fibrosis Treatment.Chembiochem : a European journal of chemical biology · 2025
    Review
  5. Review
  6. Article
  7. Advances in Cystic Fibrosis Research in Qatar: A Commentary.Journal of personalized medicine · 2023
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. MicroRNA-145 Antagonism Reverses TGF-β Inhibition of F508del CFTR Correction in Airway Epithelia.American journal of respiratory and critical care medicine · 2018
    Article
  14. Article
  15. Review
  16. Article
  17. Chlorogenic Acid Activates CFTR-Mediated Cl- Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2015
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Louise C PyleDepartment of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Jennifer C Fulton
Peter A Sloane
Kyle Backer
Marina Mazur
Jeevan Prasain
Stephen Barnes
J P Clancy
Steven M Rowe
University of Alabama at Birmingham · US

Funding

UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI David M. Bedwell · 2007 to 2026
$23.0M
PROJECT 4 - POLYPHENOLS AND DAMAGE IN THE EYEP50AT000477 · NCCIH · PURDUE UNIVERSITY WEST LAFAYETTE · PI WEAVER, CONNIE MARIE · 2000 to 2010
$15.0M
Premature Termination Codon SuppressionK23DK075788 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, STEVEN MARK · 2006 to 2010
$638k
Mechanistic Basis Underlying Protein Repair of CFTR Nonsense MutationsR03DK084110 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, STEVEN MARK · 2009 to 2010
$146k
Potentiation of Mutant CFTR ActivityF30HL096389 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PYLE, LOUISE CLARE · 2009 to 2010
$69k
NCCIH NIH HHS P50 AT00477NHLBI NIH HHS F30 HL096389NIDDK NIH HHS 1K23DK075788-01NIDDK NIH HHS 1P30DK072482-01A1NIDDK NIH HHS 1R03DK084110-01
6 · The paper itself

Abstract

Therapies to correct the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) folding defect require sensitive methods to detect channel activity in vivo. The β₂ adrenergic receptor agonists, which provide the CFTR stimuli commonly used in nasal potential difference assays, may not overcome the channel gating defects seen in ΔF508 CFTR after plasma membrane localization. In this study, we identify an agent, quercetin, that enhances the detection of surface ΔF508 CFTR, and is suitable for nasal perfusion. A screen of flavonoids in CFBE41o⁻ cells stably transduced with ΔF508 CFTR, corrected to the cell surface with low temperature growth, revealed that quercetin stimulated an increase in the short-circuit current. This increase was dose-dependent in both Fisher rat thyroid and CFBE41o⁻ cells. High concentrations inhibited Cl⁻ conductance. In CFBE41o⁻ airway cells, quercetin (20 μg/ml) activated ΔF508 CFTR, whereas the β₂ adrenergic receptor agonist isoproterenol did not. Quercetin had limited effects on cAMP levels, but did not produce detectable phosphorylation of the isolated CFTR R-domain, suggesting an activation independent of channel phosphorylation. When perfused in the nares of Cftr(+) mice, quercetin (20 μg/ml) produced a hyperpolarization of the potential difference that was absent in Cftr(-/-) mice. Finally, quercetin-induced, dose-dependent hyperpolarization of the nasal potential difference was also seen in normal human subjects. Quercetin activates CFTR-mediated anion transport in respiratory epithelia in vitro and in vivo, and may be useful in studies intended to detect the rescue of ΔF508 CFTR by nasal potential difference.

Indexed as

AnimalsBiomarkersCell MembraneChloridesCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorDose-Response Relationship, DrugDrug Evaluation, PreclinicalHumansIon Channel GatingIon TransportMembrane PotentialsMiceMutant ProteinsNasal MucosaNIH 3T3 CellsBiomarkersChloridesCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorMutant ProteinsQuercetinReceptors, Adrenergic, beta-2

Identifiers

PMID20042712
PMCPMC2970857
OpenAlexW1970103813

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.