Evidence map›Paper›PMID 21041307›Full record

ArticleThe Journal of biological chemistry2011

Identification and functional characterization of TMEM16A, a Ca2+-activated Cl- channel activated by extracellular nucleotides, in biliary epithelium.

Amal K Dutta, Al-karim Khimji, Charles Kresge, Abhijit Bugde, Michael Dougherty, Victoria Esser, Yoshiyuki Ueno, Shannon S Glaser, Gianfranco Alpini, Don C Rockey and 1 more

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 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

63 citing papers in PubMed, 102 citations in OpenAlex.

  1. Review
  2. Article
  3. Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder.American journal of physiology. Gastrointestinal and liver physiology · 2024
    Article
  4. The role of anoctamin 1 in liver disease.Journal of cellular and molecular medicine · 2024
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. The diverse roles of TMEM16A CaJournal of advanced research · 2021
    Review
  15. Review
  16. Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model.Laboratory investigation; a journal of technical methods and pathology · 2020
    Article
  17. Bicarbonate permeation through anion channels: its role in health and disease.Pflugers Archiv : European journal of physiology · 2020
    Review
  18. Article
  19. Article
  20. TMEM16A CaJournal of advanced research · 2020
    Article

3 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

11 authors at 5 institutions in 2 countries.

Amal K DuttaDepartment of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9063, USA.
Al-karim Khimji
Charles Kresge
Abhijit Bugde
Michael Dougherty
Victoria Esser
Yoshiyuki Ueno
Shannon S Glaser
Gianfranco Alpini
Don C Rockey
Andrew P Feranchak
The University of Texas Southwestern Medical Center · USCentral Texas Veterans Health Care System · USPediatrics and Genetics · USTexas A&M Health Science Center · USTohoku University · JP

Funding

GROWTH REGULATION OF THE INTRAHEPATIC BILIARY TREER01DK054811 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2000 to 2021
$3.8M
Mechanosensitive Signaling and Cholangiocyte SecretionR01DK078587 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI FERANCHAK, ANDREW P · 2008 to 2019
$3.6M
PATHOGENESIS OF HEPATIC FIBROSIS AND PORTAL HYPERTENSIONR01DK050574 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI ROCKEY, DON C. · 1996 to 2010
$3.0M
NIDDK NIH HHS DK054811NIDDK NIH HHS DK078587NIDDK NIH HHS DK50574NIDDK NIH HHS R01 DK050574NIDDK NIH HHS R01 DK054811NIDDK NIH HHS R01 DK078587
6 · The paper itself

Abstract

Cl(-) channels in the apical membrane of biliary epithelial cells (BECs) provide the driving force for ductular bile formation. Although a cystic fibrosis transmembrane conductance regulator has been identified in BECs and contributes to secretion via secretin binding basolateral receptors and increasing [cAMP](i), an alternate Cl(-) secretory pathway has been identified that is activated via nucleotides (ATP, UTP) binding apical P2 receptors and increasing [Ca(2+)](i). The molecular identity of this Ca(2+)-activated Cl(-) channel is unknown. The present studies in human, mouse, and rat BECs provide evidence that TMEM16A is the operative channel and contributes to Ca(2+)-activated Cl(-) secretion in response to extracellular nucleotides. Furthermore, Cl(-) currents measured from BECs isolated from distinct areas of intrahepatic bile ducts revealed important functional differences. Large BECs, but not small BECs, exhibit cAMP-stimulated Cl(-) currents. However, both large and small BECs express TMEM16A and exhibit Ca(2+)-activated Cl(-) efflux in response to extracellular nucleotides. Incubation of polarized BEC monolayers with IL-4 increased TMEM16A protein expression, membrane localization, and transepithelial secretion (I(sc)). These studies represent the first molecular identification of an alternate, noncystic fibrosis transmembrane conductance regulator, Cl(-) channel in BECs and suggest that TMEM16A may be a potential target to modulate bile formation in the treatment of cholestatic liver disorders.

Indexed as

AnimalsAnoctamin-1BileBiliary TractCell Membrane PermeabilityChloride ChannelsChlorineEpitheliumExtracellular SpaceGene Expression RegulationHumansInterleukin-4Membrane ProteinsMiceNeoplasm ProteinsNucleotidesANO1 protein, humanAnoctamin-1Chloride ChannelsChlorineInterleukin-4Membrane ProteinsNeoplasm ProteinsNucleotidesRNA, Messenger

Identifiers

PMID21041307
PMCPMC3013035
OpenAlexW2092007358

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.