Evidence map›Paper›PMID 21914796›Full record

ArticleThe Journal of biological chemistry2011

Novel role for pendrin in orchestrating bicarbonate secretion in cystic fibrosis transmembrane conductance regulator (CFTR)-expressing airway serous cells.

James P Garnett, Emma Hickman, Rachel Burrows, Péter Hegyi, László Tiszlavicz, Alan W Cuthbert, Peying Fong, Michael A Gray

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

68 citing papers in PubMed, 97 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. SLC26 Anion Transporters.Handbook of experimental pharmacology · 2024
    Review
  5. Dynamic regulation of airway surface liquid pH by TMEM16A and SLC26A4 in cystic fibrosis nasal epithelia with rare mutations.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Case report: A case ofFrontiers in pediatrics · 2022
    Article
  14. Review
  15. Article
  16. Article
  17. Impaired Renal HCOJournal of the American Society of Nephrology : JASN · 2020
    Article
  18. Bicarbonate permeation through anion channels: its role in health and disease.Pflugers Archiv : European journal of physiology · 2020
    Review
  19. Expression of ClEuropean archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2020
    Article
  20. TNFα and IL-17 alkalinize airway surface liquid through CFTR and pendrin.American journal of physiology. Cell physiology · 2020
    Article

8 more citing papers are in PubMed but not listed here.

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

8 authors at 5 institutions in 4 countries.

James P GarnettInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
Emma Hickman
Rachel Burrows
Péter Hegyi
László Tiszlavicz
Alan W Cuthbert
Peying Fong
Michael A Gray
Kansas State University · USNovartis (Switzerland) · CHUniversity of Szeged · HUNewcastle University · GBUniversity of Cambridge · GB

Funding

Biotechnology and Biological Sciences Research Council BBS/S/M/2006/13134
6 · The paper itself

Abstract

In most HCO(3)(-)-secreting epithelial tissues, SLC26 Cl(-)/HCO(3)(-) transporters work in concert with the cystic fibrosis transmembrane conductance regulator (CFTR) to regulate the magnitude and composition of the secreted fluid, a process that is vital for normal tissue function. By contrast, CFTR is regarded as the only exit pathway for HCO(3)(-) in the airways. Here we show that Cl(-)/HCO(3)(-) anion exchange makes a major contribution to transcellular HCO(3)(-) transport in airway serous cells. Real-time measurement of intracellular pH from polarized cultures of human Calu-3 cells demonstrated cAMP/PKA-activated Cl(-)-dependent HCO(3)(-) transport across the luminal membrane via CFTR-dependent coupled Cl(-)/HCO(3)(-) anion exchange. The pharmacological and functional profile of the luminal anion exchanger was consistent with SLC26A4 (pendrin), which was shown to be expressed by quantitative RT-PCR, Western blot, and immunofluorescence. Pendrin-mediated anion exchange activity was confirmed by shRNA pendrin knockdown (KD), which markedly reduced cAMP-activated Cl(-)/HCO(3)(-) exchange. To establish the relative roles of CFTR and pendrin in net HCO(3)(-) secretion, transepithelial liquid secretion rate and liquid pH were measured in wild type, pendrin KD, and CFTR KD cells. cAMP/PKA increased the rate and pH of the secreted fluid. Inhibiting CFTR reduced the rate of liquid secretion but not the pH, whereas decreasing pendrin activity lowered pH with little effect on volume. These results establish that CFTR predominately controls the rate of liquid secretion, whereas pendrin regulates the composition of the secreted fluid and identifies a critical role for this anion exchanger in transcellular HCO(3)(-) secretion in airway serous cells.

Indexed as

Gene Expression RegulationAnimalsBicarbonatesBody FluidsCell Line, TumorChloride-Bicarbonate AntiportersChloridesCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGene Knockdown TechniquesHumansHydrogen-Ion ConcentrationMembrane Transport ProteinsRatsBicarbonatesChloride-Bicarbonate AntiportersChloridesCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorMembrane Transport ProteinsSLC26A4 protein, humanSulfate Transporters

Identifiers

PMID21914796
PMCPMC3220502
OpenAlexW1973420791

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.