Evidence map›Paper›PMID 21034448›Full record

ArticleRespiratory research2010

Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium.

Guoqing Wang, Rui Wang, Barbara Ferris, Jacqueline Salit, Yael Strulovici-Barel, Neil R Hackett, Ronald G Crystal

2 registry-linked trialsOpen access · goldAbstract read
In one paragraph

Article in Respiratory research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.9field-weighted citation impact, top 24% 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.

NCT00224185 completednot on this map

Evaluation of the Lungs of Normal Individuals With Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing and Bronchial Wall Biopsy

TypeobservationalSponsorWeill Medical College of Cornell UniversityRan2004 to 2012Enrolled196ConditionsSmoking, Lung DiseasesArmsBronchopulmonary Lung Lavage, Bronchial Brushing, Bronchial Wall Biopsy
NCT00224198 completednot on this map

Evaluation of the Lungs of Individuals With Lung Disease With Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing and Bronchial Wall Biopsy

TypeobservationalSponsorWeill Medical College of Cornell UniversityRan2004 to 2012Enrolled196ConditionsLung Disease, Bronchitis, Emphysema, COPDArmsLung Disease
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. The limbic and extra-limbic encephalitis associated with glutamic acid decarboxylase (GAD)-65 antibodies: an observational study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Observational
  4. Article
  5. Review
  6. Bioinformatic Analysis ofMembranes · 2021
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro.American journal of respiratory cell and molecular biology · 2014
    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

7 authors at 1 institution in 1 country.

Guoqing WangDepartment of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
Rui Wang
Barbara Ferris
Jacqueline Salit
Yael Strulovici-Barel
Neil R Hackett
Ronald G Crystal
Cornell University · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024996 · NCRR · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2007 to 2011
$49.6M
Role of Alveolar Macrophages in the Accelerated Emphysema of HIV-1 PositiveP50HL084936 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CRYSTAL, RONALD G · 2007 to 2011
$14.2M
Candidate Genes for Susceptibility to BronchitisR01HL074326 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CRYSTAL, RONALD G · 2004 to 2007
$2.4M
NCRR NIH HHS UL1-RR024996NHLBI NIH HHS P50 HL084936NHLBI NIH HHS R01 HL074326
6 · The paper itself

Abstract

backgroundThe production of gamma-amino butyric acid (GABA) is dependent on glutamate decarboxylases (GAD65 and GAD67), the enzymes that catalyze the decarboxylation of glutamate to GABA. Based on studies suggesting a role of the airway epithelial GABAergic system in asthma-related mucus overproduction, we hypothesized that cigarette smoking, another disorder associated with increased mucus production, may modulate GABAergic system-related gene expression levels in the airway epithelium.

methodsWe assessed expression of the GABAergic system in human airway epithelium obtained using bronchoscopy to sample the epithelium and microarrays to evaluate gene expression. RT-PCR was used to confirm gene expression of GABAergic system gene in large and small airway epithelium from heathy nonsmokers and healthy smokers. The differences in the GABAergic system gene was further confirmed by TaqMan, immunohistochemistry and Western analysis.

resultsThe data demonstrate there is a complete GABAergic system expressed in the large and small human airway epithelium, including glutamate decarboxylase, GABA receptors, transporters and catabolism enzymes. Interestingly, of the entire GABAergic system, smoking modified only the expression of GAD67, with marked up-regulation of GAD67 gene expression in both large (4.1-fold increase, p < 0.01) and small airway epithelium of healthy smokers (6.3-fold increase, p < 0.01). At the protein level, Western analysis confirmed the increased expression of GAD67 in airway epithelium of healthy smokers compared to healthy nonsmokers (p < 0.05). There was a significant positive correlation between GAD67 and MUC5AC gene expression in both large and small airway epithelium (p < 0.01), implying a link between GAD67 and mucin overproduction in association with smoking.

conclusionsIn the context that GAD67 is the rate limiting enzyme in GABA synthesis, the correlation of GAD67 gene expression with MUC5AC expressions suggests that the up-regulation of airway epithelium expression of GAD67 may contribute to the increase in mucus production observed in association with cigarette smoking.

trial registrationNCT00224198; NCT00224185.

Indexed as

AdultFemaleGlutamate DecarboxylaseHumansLungMaleMucin 5ACRespiratory MucosaSmokingTissue DistributionUp-RegulationGlutamate Decarboxylaseglutamate decarboxylase 1MUC5AC protein, humanMucin 5AC

Identifiers

PMID21034448
PMCPMC2988726
OpenAlexW2170059505

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.