Evidence map›Paper›PMID 30385725›Full record

ArticleJCI insight2018

Arhgef12 drives IL17A-induced airway contractility and airway hyperresponsiveness in mice.

Valerie Fong, Austin Hsu, Esther Wu, Agnieszka P Looney, Previn Ganesan, Xin Ren, Dean Sheppard, Sarah A Wicher, Michael A Thompson, Rodney D Britt and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.4field-weighted citation impact, top 35% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Asthma endotypes and theratypes.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
  3. Article
  4. Review
  5. Molecular mechanism of bitter taste receptor agonist-mediated relaxation of airway smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
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

12 authors at 4 institutions in 1 country.

Valerie FongDivision of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Austin HsuGladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
Esther WuDivision of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Agnieszka P LooneyDivision of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Previn GanesanDivision of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Xin RenDivision of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Dean SheppardDivision of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Sarah A WicherDepartment of Physiology and Biomedical Engineering and.
Michael A ThompsonDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Rodney D BrittCenter for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Y S PrakashDepartment of Physiology and Biomedical Engineering and.
Mallar BhattacharyaDivision of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USMayo Clinic · USGladstone Institutes · USNationwide Children's Hospital · US

Funding

Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1M
UC BRAID Center for Accelerated Innovation COVID-19 diagnostic project developmentU54HL119893 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PALAZZOLO, MICHAEL J · 2013 to 2020
$18.3M
Neurotrophins in the LungR01HL088029 · NHLBI · MAYO CLINIC ROCHESTER · PI PRAKASH, Y. S. · 2009 to 2022
$5.9M
The Regulation of RhoA Activation in Airway Smooth MuscleR01HL131560 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BHATTACHARYA, MALLAR · 2016 to 2020
$1.9M
Enhancing Corticosteroid Sensitivity in Neonatal and Pediatric Lung DiseaseR00HL131682 · NHLBI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI BRITT, RODNEY · 2018 to 2020
$845k
NCATS NIH HHS UL1 TR001872NHLBI NIH HHS R00 HL131682NHLBI NIH HHS R01 HL088029NHLBI NIH HHS R01 HL131560NHLBI NIH HHS U54 HL119893
6 · The paper itself

Abstract

Patients with severe, treatment-refractory asthma are at risk for death from acute exacerbations. The cytokine IL17A has been associated with airway inflammation in severe asthma, and novel therapeutic targets within this pathway are urgently needed. We recently showed that IL17A increases airway contractility by activating the procontractile GTPase RhoA. Here, we explore the therapeutic potential of targeting the RhoA pathway activated by IL17A by inhibiting RhoA guanine nucleotide exchange factors (RhoGEFs), intracellular activators of RhoA. We first used a ribosomal pulldown approach to profile mouse airway smooth muscle by qPCR and identified Arhgef12 as highly expressed among a panel of RhoGEFs. ARHGEF12 was also the most highly expressed RhoGEF in patients with asthma, as found by RNA sequencing. Tracheal rings from Arhgef12-KO mice and WT rings treated with a RhoGEF inhibitor had evidence of decreased contractility and RhoA activation in response to IL17A treatment. In a house dust mite model of allergic sensitization, Arhgef12-KO mice had decreased airway hyperresponsiveness without effects on airway inflammation. Taken together, our results show that Arhgef12 is necessary for IL17A-induced airway contractility and identify a therapeutic target for severe asthma.

Indexed as

AgedAnimalsAsthmaDisease ProgressionFemaleGuanine Nucleotide Exchange FactorsHumansInterleukin-17MaleMiceMiddle AgedMuscle ContractionRespiratory HypersensitivityrhoA GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsSequence Analysis, RNAArhgef12 protein, mouseGuanine Nucleotide Exchange FactorsInterleukin-17rhoA GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsAsthmaMuscle BiologyPulmonology

Identifiers

PMID30385725
PMCPMC6238747
OpenAlexW2899374476

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.