Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions

Fibroblast growth factor 23 and Klotho contribute to airway inflammation

Stefanie Krick, Alexander Grabner, Nathalie Baumlin, Christopher Yanucil, Scott Helton, Astrid Grosche, Juliette Sailland, Patrick Geraghty, Liliana Viera, Derek W. Russell, J. Michael Wells, Xin Xu, Amit Gaggar, Jarrod Barnes, Gwendalyn D. King, Michael Campos, Christian Faul, Matthias Salathe
European Respiratory Journal 2018 52: 1800236; DOI: 10.1183/13993003.00236-2018
Stefanie Krick
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Grabner
2Division of Nephrology, Dept of Medicine, Duke University Medical Center, Duke University, Durham, NC, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathalie Baumlin
3Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher Yanucil
4Division of Nephrology, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott Helton
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Astrid Grosche
3Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juliette Sailland
3Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Geraghty
5Division of Pulmonary and Critical Care Medicine, Dept of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liliana Viera
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derek W. Russell
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Michael Wells
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
6UAB Lung Health Center, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xin Xu
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amit Gaggar
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jarrod Barnes
1Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gwendalyn D. King
7Dept of Neurobiology, The University of Alabama at Birmingham, Birmingham, AL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Campos
3Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian Faul
4Division of Nephrology, Dept of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
8Both senior authors contributed equally to this work
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias Salathe
3Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
8Both senior authors contributed equally to this work
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Circulating levels of fibroblast growth factor (FGF)23 are associated with systemic inflammation and increased mortality in chronic kidney disease. α-Klotho, a co-receptor for FGF23, is downregulated in chronic obstructive pulmonary disease (COPD). However, whether FGF23 and Klotho-mediated FGF receptor (FGFR) activation delineates a pathophysiological mechanism in COPD remains unclear. We hypothesised that FGF23 can potentiate airway inflammation via Klotho-independent FGFR4 activation.

FGF23 and its effect were studied using plasma and transbronchial biopsies from COPD and control patients, and primary human bronchial epithelial cells isolated from COPD patients as well as a murine COPD model.

Plasma FGF23 levels were significantly elevated in COPD patients. Exposure of airway epithelial cells to cigarette smoke and FGF23 led to a significant increase in interleukin-1β release via Klotho-independent FGFR4-mediated activation of phospholipase Cγ/nuclear factor of activated T-cells signalling. In addition, Klotho knockout mice developed COPD and showed airway inflammation and elevated FGFR4 expression in their lungs, whereas overexpression of Klotho led to an attenuation of airway inflammation.

Cigarette smoke induces airway inflammation by downregulation of Klotho and activation of FGFR4 in the airway epithelium in COPD. Inhibition of FGF23 or FGFR4 might serve as a novel anti-inflammatory strategy in COPD.

Abstract

Fibroblast growth factor 23 and cigarette smoke-induced FGFR4 signalling lead to the development of airway inflammation and emphysema http://ow.ly/j4tZ30jWyGF

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • Conflict of interest: None declared.

  • Support statement: This work was supported by the Flight Attendant Medical Research Institute (YFAC152003 to S. Krick, YCSA113380 to P. Geraghty and CIA13033 to M. Salathe), the Cystic Fibrosis Foundation (CFF KRICK1610 to S. Krick and SALATH14G0 to M. Salathe), the American Heart Association (A. Grabner and C. Faul), the American Diabetes Association (C. Faul), the James and Esther King Florida Biomedical Research Program (5JK02 to M. Salathe) and the National Institutes of Health (R01HL128714 to C. Faul). Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received July 15, 2017.
  • Accepted April 27, 2018.
  • Copyright ©ERS 2018
View Full Text
PreviousNext
Back to top
View this article with LENS
Vol 52 Issue 1 Table of Contents
European Respiratory Journal: 52 (1)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Fibroblast growth factor 23 and Klotho contribute to airway inflammation
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Fibroblast growth factor 23 and Klotho contribute to airway inflammation
Stefanie Krick, Alexander Grabner, Nathalie Baumlin, Christopher Yanucil, Scott Helton, Astrid Grosche, Juliette Sailland, Patrick Geraghty, Liliana Viera, Derek W. Russell, J. Michael Wells, Xin Xu, Amit Gaggar, Jarrod Barnes, Gwendalyn D. King, Michael Campos, Christian Faul, Matthias Salathe
European Respiratory Journal Jul 2018, 52 (1) 1800236; DOI: 10.1183/13993003.00236-2018

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Fibroblast growth factor 23 and Klotho contribute to airway inflammation
Stefanie Krick, Alexander Grabner, Nathalie Baumlin, Christopher Yanucil, Scott Helton, Astrid Grosche, Juliette Sailland, Patrick Geraghty, Liliana Viera, Derek W. Russell, J. Michael Wells, Xin Xu, Amit Gaggar, Jarrod Barnes, Gwendalyn D. King, Michael Campos, Christian Faul, Matthias Salathe
European Respiratory Journal Jul 2018, 52 (1) 1800236; DOI: 10.1183/13993003.00236-2018
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Abstract
    • Introduction
    • Methods
    • Results
    • Discussion
    • Supplementary material
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Subjects

  • Mechanisms of lung disease
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

Original articles

  • Identifying early PAH biomarkers in systemic sclerosis
  • Viable virus aerosol propagation by PAP circuit leak
  • Ambulatory management of secondary spontaneous pneumothorax
Show more Original articles

Basic science

  • Antimicrobial peptide S100A8/A9 as a regulator of macrophage phenotype and function
  • Insights into surfactant protein C trafficking
  • Alveolar type 2 cells enriched in PD-L1 and expanded following pneumonectomy
Show more Basic science

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Reviewers
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2022 by the European Respiratory Society