Evidence map›Paper›PMID 24944194›Full record

ArticleScience translational medicine2014

Selective targeting of TGF-β activation to treat fibroinflammatory airway disease.

Shunsuke Minagawa, Jianlong Lou, Robert I Seed, Anthony Cormier, Shenping Wu, Yifan Cheng, Lynne Murray, Ping Tsui, Jane Connor, Ronald Herbst and 22 more

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

Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 88 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. A tumor-specific mechanism of TScience immunology · 2021
    Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  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

32 authors at 1 institution in 1 country.

Shunsuke MinagawaDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Jianlong LouDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA.
Robert I SeedDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Anthony CormierDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Shenping WuThe Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94110, USA.
Yifan ChengThe Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94110, USA.
Lynne MurrayDepartment of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, MD 20878, USA. Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Cambridge CB21 6GH, UK.
Ping TsuiDepartment of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, MD 20878, USA.
Jane ConnorDepartment of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, MD 20878, USA.
Ronald HerbstDepartment of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, MD 20878, USA.
Cedric GovaertsDepartment of Respiratory, Inflammation and Autoimmunity, MedImmune, Cambridge CB21 6GH, UK.
Tyren BarkerDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Stephanie CambierDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Haruhiko YanagisawaDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Amanda GoodsellDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
Mitsuo HashimotoDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Oliver J BrandDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Ran ChengDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Royce MaDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Kate J McKnellyDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Weihua WenDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA.
Arthur HillDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94110, USA.
David JablonsDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94110, USA.
Paul WoltersDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
Hideya KitamuraDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
Jun ArayaDepartment of Pulmonary Medicine, Jikei University, Tokyo 105 8461, Japan.
Andrea J BarczakDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
David J ErleDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
Louis F ReichardtGenetics, Development, and Behavioral Sciences, University of California, San Francisco, San Francisco, CA 94110, USA.
James D MarksDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA.
Jody L BaronDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
Stephen L NishimuraDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA. stephen.nishimura@ucsf.edu.
University of California, San Francisco · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
Underlying mechanisms for the pro-angiogenic phenotype of AVMsP01NS044155 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SU, HUA · 2003 to 2013
$12.8M
Integrin avB8 Inhibits Airway Epithelial Cell GrowthR01HL063993 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2001 to 2011
$3.3M
Role of genetic variation in TGF-beta overactivation in COPDR01HL113032 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2012 to 2015
$2.1M
Role of Squamous Metaplasia in Small Airways Disease in COPDR01HL090662 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NISHIMURA, STEPHEN L · 2009 to 2010
$953k
NHLBI NIH HHS HL063993NHLBI NIH HHS HL090662NHLBI NIH HHS HL113032NHLBI NIH HHS R01 HL063993NHLBI NIH HHS R01 HL090662NHLBI NIH HHS R01 HL113032NIDDK NIH HHS P30 DK026743NIDDK NIH HHS P30DK026743NINDS NIH HHS NS044155NINDS NIH HHS P01 NS044155
6 · The paper itself

Abstract

Airway remodeling, caused by inflammation and fibrosis, is a major component of chronic obstructive pulmonary disease (COPD) and currently has no effective treatment. Transforming growth factor-β (TGF-β) has been widely implicated in the pathogenesis of airway remodeling in COPD. TGF-β is expressed in a latent form that requires activation. The integrin αvβ8 (encoded by the itgb8 gene) is a receptor for latent TGF-β and is essential for its activation. Expression of integrin αvβ8 is increased in airway fibroblasts in COPD and thus is an attractive therapeutic target for the treatment of airway remodeling in COPD. We demonstrate that an engineered optimized antibody to human αvβ8 (B5) inhibited TGF-β activation in transgenic mice expressing only human and not mouse ITGB8. The B5 engineered antibody blocked fibroinflammatory responses induced by tobacco smoke, cytokines, and allergens by inhibiting TGF-β activation. To clarify the mechanism of action of B5, we used hydrodynamic, mutational, and electron microscopic methods to demonstrate that αvβ8 predominantly adopts a constitutively active, extended-closed headpiece conformation. Epitope mapping and functional characterization of B5 revealed an allosteric mechanism of action due to locking-in of a low-affinity αvβ8 conformation. Collectively, these data demonstrate a new model for integrin function and present a strategy to selectively target the TGF-β pathway to treat fibroinflammatory airway diseases.

Indexed as

AnimalsHumansMiceMice, TransgenicTracheitisTransforming Growth Factor betaTransforming Growth Factor beta

Identifiers

PMID24944194
PMCPMC4341974
OpenAlexW2144222001

What OpenQuestion holds

Textmetadata
LicenceTDM
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.