Evidence map›Paper›PMID 37435075›Full record

ArticleFrontiers in immunology2023

Transforming growth factor-β1 and SMAD signalling pathway in the small airways of smokers and patients with COPD: potential role in driving fibrotic type-2 epithelial mesenchymal transition.

Samuel James Brake, Wenying Lu, Collin Chia, Greg Haug, Josie Larby, Ashutosh Hardikar, Gurpreet K Singhera, Tillie L Hackett, Mathew Suji Eapen, Sukhwinder Singh Sohal

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 21 citations in OpenAlex.

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  9. LAMC2 Drives Airway Remodeling in COPD via EMT Regulation Through the AKT Pathway.International journal of chronic obstructive pulmonary disease · 2026
    Article
  10. Review
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  12. Prognostic Value of Biomarkers in Chronic Obstructive Pulmonary Disease: A Comprehensive Review.International journal of chronic obstructive pulmonary disease · 2025
    Review
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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

10 authors at 5 institutions in 2 countries.

Samuel James BrakeRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
Wenying LuRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
Collin ChiaRespiratory Medicine, Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia.
Greg HaugDepartment of Respiratory Medicine, Launceston General Hospital, Launceston, TAS, Australia.
Josie LarbyDepartment of Respiratory Medicine, Launceston General Hospital, Launceston, TAS, Australia.
Ashutosh HardikarDepartment of Cardiothoracic Surgery, Royal Hobart Hospital, Hobart, TAS, Australia.
Gurpreet K SingheraDepartment of Anaesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Tillie L HackettDepartment of Anaesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Mathew Suji EapenRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
Sukhwinder Singh SohalRespiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
Launceston General Hospital · AUUniversity of Tasmania · AURoyal Hobart Hospital · AUSt. Paul's Hospital · CAUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: COPD is a common disease characterized by respiratory airflow obstruction. TGF-β1 and SMAD pathway is believed to play a role in COPD pathogenesis by driving epithelial mesenchymal transition (EMT). Methods: We investigated TGF-β1 signalling and pSmad2/3 and Smad7 activity in resected small airway tissue from patients with; normal lung function and a smoking history (NLFS), current smokers and ex-smokers with COPD GOLD stage 1 and 2 (COPD-CS and COPD-ES) and compared these with normal non-smoking controls (NC). Using immunohistochemistry, we measured activity for these markers in the epithelium, basal epithelium, and reticular basement membrane (RBM). Tissue was also stained for EMT markers E-cadherin, S100A4 and vimentin. Results: The Staining of pSMAD2/3 was significantly increased in the epithelium, and RBM of all COPD groups compared to NC (p <0.0005). There was a less significant increase in COPD-ES basal cell numbers compared to NC (p= 0.02). SMAD7 staining showed a similar pattern (p <0.0001). All COPD group levels of TGF-β1 in the epithelium, basal cells, and RBM cells were significantly lower than NC (p <0.0001). Ratio analysis showed a disproportionate increase in SMAD7 levels compared to pSMAD2/3 in NLFS, COPD-CS and COPD-ES. pSMAD negatively correlated with small airway calibre (FEF Conclusion: Activation of the SMAD pathway via pSMAD2/3 is triggered by smoking and active in patients with mild to moderate COPD. These changes correlated to decline in lung function. Activation of the SMADs in the small airways is independent of TGF-β1, suggesting factors other than TGF-β1 are driving these pathways. These factors may have implications for small airway pathology in smokers and COPD through the process of EMT, however more mechanistic work is needed to prove these correlations.

Indexed as

Airway ObstructionPulmonary Disease, Chronic ObstructiveSmad ProteinsTransforming Growth Factor beta1Epithelial-Mesenchymal TransitionHumansSignal TransductionSmokersSmad ProteinsTransforming Growth Factor beta1COPD - chronic obstructive pulmonary diseaseepithelial to mesenchymal transitionsmall airwaysmokingTGF — transforming growth factor

Identifiers

PMID37435075
PMCPMC10331458
OpenAlexW4382058861

What OpenQuestion holds

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LicenceCC BY
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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.