Evidence map›Paper›PMID 29071730›Full record

ArticleThe Journal of physiology2018

Transforming growth factor-β enhances Rho-kinase activity and contraction in airway smooth muscle via the nucleotide exchange factor ARHGEF1.

Yasin Shaifta, Charles E MacKay, Nneka Irechukwu, Katie A O'Brien, David B Wright, Jeremy P T Ward, Greg A Knock

Open access · hybridAbstract read
In one paragraph

Article in The Journal of physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.0field-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.

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

20 citing papers in PubMed, 24 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. GRespiratory research · 2024
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Airway smooth muscle tone increases actin filamentogenesis and contractile capacity.American journal of physiology. Lung cellular and molecular physiology · 2020
    Article
  15. Review
  16. Article
  17. Transforming Growth Factor-β1 Decreases βAmerican journal of respiratory cell and molecular biology · 2019
    Article
  18. Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma.American journal of physiology. Lung cellular and molecular physiology · 2019
    Article
  19. Review
  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.

Yasin ShaiftaDivision of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine, King's College London, London, SE1 1UL, UK.
Charles E MacKayDivision of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine, King's College London, London, SE1 1UL, UK.
Nneka IrechukwuDivision of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine, King's College London, London, SE1 1UL, UK.
Katie A O'BrienDivision of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine, King's College London, London, SE1 1UL, UK.
David B WrightDivision of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine, King's College London, London, SE1 1UL, UK.
Jeremy P T WardDivision of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine, King's College London, London, SE1 1UL, UK.ORCID 0000-0001-7037-4268
Greg A KnockDivision of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine, King's College London, London, SE1 1UL, UK.ORCID 0000-0002-6018-0360
King's College London · GB

Funding

British Heart Foundation FS/12/43/29608Wellcome Trust 087776
6 · The paper itself

Abstract

key pointsTransforming growth-factor-β (TGF-β) and RhoA/Rho-kinase are independently implicated in the airway hyper-responsiveness associated with asthma, but how these proteins interact is not fully understood. We examined the effects of pre-treatment with TGF-β on expression and activity of RhoA, Rho-kinase and ARHGEF1, an activator of RhoA, as well as on bradykinin-induced contraction, in airway smooth muscle. TGF-β enhanced bradykinin-induced RhoA translocation, Rho-kinase-dependent phosphorylation and contraction, but partially suppressed bradykinin-induced RhoA activity (RhoA-GTP content). TGF-β enhanced the expression of ARHGEF1, while a small interfering RNA against ARHGEF1 and a RhoGEF inhibitor prevented the effects of TGF-β on RhoA and Rho-kinase activity and contraction, respectively. ARHGEF1 expression was also enhanced in airway smooth muscle from asthmatic patients and ovalbumin-sensitized mice. ARHGEF1 is a key TGF-β target gene, an important regulator of Rho-kinase activity and therefore a potential therapeutic target for the treatment of asthmatic airway hyper-responsiveness. ABSTRACT: Transforming growth factor-β (TGF-β), RhoA/Rho-kinase and Src-family kinases (SrcFK) have independently been implicated in airway hyper-responsiveness, but how they interact to regulate airway smooth muscle contractility is not fully understood. We found that TGF-β pre-treatment enhanced acute contractile responses to bradykinin (BK) in isolated rat bronchioles, and inhibitors of RhoGEFs (Y16) and Rho-kinase (Y27632), but not the SrcFK inhibitor PP2, prevented this enhancement. In cultured human airway smooth muscle cells (hASMCs), TGF-β pre-treatment enhanced the protein expression of the Rho guanine nucleotide exchange factor ARHGEF1, MLC

Indexed as

Muscle ContractionAdultAnimalsAsthmaCase-Control StudiesCells, CulturedFemaleGene Expression RegulationHumansMaleMiceMiddle AgedMuscle, SmoothPhosphorylationRatsRats, WistarrhoA GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsTransforming Growth Factor betaairway smooth muscleRho-kinaseTGF-β

Identifiers

PMID29071730
PMCPMC5746525
OpenAlexW2765881497

What OpenQuestion holds

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Registered trials

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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.