Evidence map›Paper›PMID 22988107›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.

Fen Huang, Hongkang Zhang, Meng Wu, Huanghe Yang, Makoto Kudo, Christian J Peters, Prescott G Woodruff, Owen D Solberg, Matthew L Donne, Xiaozhu Huang and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers.

0numbers the graph read from it
0cells of the map it votes in
206citing papers in PubMed
13.3field-weighted citation impact, top 1% 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

206 citing papers in PubMed, 339 citations in OpenAlex.

  1. Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2024
    Trial
  2. Trial
  3. Review
  4. Review
  5. Pacemaking in the lymphatic system.The Journal of physiology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Interplay of CaThe Journal of physiology · 2026
    Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. [Transmembrane protein 16A--a new target for the treatment of airway inflammatory diseases].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025
    Review
  17. Article
  18. Channeling Relaxation through Multiple Means: TMEM16A Antagonism for Asthma.American journal of respiratory cell and molecular biology · 2025
    Article
  19. Article
  20. Article

146 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

19 authors at 6 institutions in 2 countries.

Fen HuangHoward Hughes Medical Institute and Department of Physiology, University of California, San Francisco, CA 94158, USA.
Hongkang Zhang
Meng Wu
Huanghe Yang
Makoto Kudo
Christian J Peters
Prescott G Woodruff
Owen D Solberg
Matthew L Donne
Xiaozhu Huang
Dean Sheppard
John V Fahy
Paul J Wolters
Brigid L M Hogan
Walter E Finkbeiner
Min Li
Yuh-Nung Jan
Lily Yeh Jan
Jason R Rock
University of California, San Francisco · USHoward Hughes Medical Institute · USJohns Hopkins University · USApath (United States) · USDuke Medical Center · USHigh Throughput Biology (United States) · US

Funding

Role of miRNAs in Th2-Driven inflammation in AsthmaP01HL107202 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAHY, JOHN V · 2012 to 2023
$23.3M
Johns Hopkins Ion Channel CenterU54MH084691 · NIMH · JOHNS HOPKINS UNIVERSITY · PI LI, MIN · 2008 to 2012
$13.9M
PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
Molecular, Genetic & Physiological Studies of Calcium-activated Chloride ChannelsR01NS069229 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAN, LILY Y · 2011 to 2020
$3.5M
Development of Bioactive Chemical Probes for Calcium-activated Chloride ChannelR03DA031670 · NIDA · JOHNS HOPKINS UNIVERSITY · PI LI, MIN · 2011 to 2012
$82k
Howard Hughes Medical InstituteNHLBI NIH HHS P01 HL107202NICHD NIH HHS T32 HD007470NICHD NIH HHS T32HD007470NIDA NIH HHS R03 DA031670NIDA NIH HHS R03DA031670NIMH NIH HHS U54 MH084691NIMH NIH HHS U54MH084691NINDS NIH HHS R01 NS069229
6 · The paper itself

Abstract

Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in the adult airway surface epithelium and ASM. The epithelial expression is increased in asthmatics, particularly in secretory cells. Based on this and the proposed functions of CaCC, we hypothesized that TMEM16A inhibitors would negatively regulate both epithelial mucin secretion and ASM contraction. We used a high-throughput screen to identify small-molecule blockers of TMEM16A-CaCC channels. We show that inhibition of TMEM16A-CaCC significantly impairs mucus secretion in primary human airway surface epithelial cells. Furthermore, inhibition of TMEM16A-CaCC significantly reduces mouse and human ASM contraction in response to cholinergic agonists. TMEM16A-CaCC blockers, including those identified here, may positively impact multiple causes of asthma symptoms.

Indexed as

AnimalsAnoctamin-1Cells, CulturedChloride ChannelsEpithelial CellsHumansImmunohistochemistryMiceMicroscopy, FluorescenceMucinsMuscle ContractionMuscle, SmoothRespiratory SystemANO1 protein, mouseAnoctamin-1Chloride ChannelsMucins

Identifiers

PMID22988107
PMCPMC3479591
OpenAlexW2095655618

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.