Skip to main content

Main menu

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

Balancing TGFbeta/BMP in pulmonary arterial hypertension

Nina Rol, Robert Szulcek, Marie-José Goumans, Chris Dickhoff, Anton Vonk-Noordegraaf, Harm Jan Bogaard, Geerten Van Nieuw Amerongen
European Respiratory Journal 2015 46: PA4903; DOI: 10.1183/13993003.congress-2015.PA4903
Nina Rol
1Department of Pulmonary Medicine, VU University Medical Center, Amsterdam, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Szulcek
1Department of Pulmonary Medicine, VU University Medical Center, Amsterdam, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie-José Goumans
2Department of Molecular Cell Biology, LUMC, Leiden, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chris Dickhoff
3Department of Surgery, VU University Medical Center, Amsterdam, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anton Vonk-Noordegraaf
1Department of Pulmonary Medicine, VU University Medical Center, Amsterdam, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Harm Jan Bogaard
1Department of Pulmonary Medicine, VU University Medical Center, Amsterdam, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Geerten Van Nieuw Amerongen
4Department of Physiology, VU University Medical Center, Amsterdam, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
Loading

Abstract

Introduction: Hemodynamic alterations contribute to disease progression in Pulmonary Arterial Hypertension (PAH), a deadly lung disease associated with mutations in the Transofrming Growth Factor beta (TGFb) –Superfamily. Mutations of the bone morphogenetic protein receptor 2 (BMPR2) and increased expression of TGFb support the idea for a central role of TGFb/BMP imbalance in PAH. Therefore we investigated whether shear stress induces dysfunctional TGFb/BMP responses in pulmonary microvascular endothelial cells (MVEC) from PAH patients.

Methods: Control MVECs from cancer lobectomies were compared to PAH MVECs isolated from autopsy and transplantation biopsies. Confluent cells were stimulated with TGFb1 or BMP9 or subjected to shear stress, and downstream phosphorylation of Smad2/3 and Smad1/5 was quantified. Reversal of shear stress induced responses was tested by addition of TGFb neutralizing antibody 1D11 and the selective inhibitor of the BMP type I receptor kinases LDN-193189.

Results: Both control and PAH MVECs showed an increased phosphorylation of Smad2/3 upon TGFb1 and shear stress stimulation, which was blocked by 1D11. Suprisingly, BMPR2 mediated responses appeared to be intact and led to increased phosphorylation of Smad1/5 when exposed to BMP9 and shear stress, which was inhibited in presence of LDN-193189.

Conclusions: Under the in vitro conditions used, both TGFb and BMP mediated signaling is intact in PAH MVECs. Upon exposure to shear stress or ligand stimulation, control and PAH MVECs showed no differences in downstream signaling of the TGFb/BMP pathway. The effective inhibition of Smad phosphorylation during shear stress shows the importance of TGFb ligands and BMPRI with regards to shear adaptation in MVECs.

  • Pulmonary hypertension
  • Cell biology
  • Physiology
  • Copyright ©ERS 2015
Previous
Back to top
Vol 46 Issue suppl 59 Table of Contents
  • 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.
Balancing TGFbeta/BMP in pulmonary arterial hypertension
(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.
Citation Tools
Balancing TGFbeta/BMP in pulmonary arterial hypertension
Nina Rol, Robert Szulcek, Marie-José Goumans, Chris Dickhoff, Anton Vonk-Noordegraaf, Harm Jan Bogaard, Geerten Van Nieuw Amerongen
European Respiratory Journal Sep 2015, 46 (suppl 59) PA4903; DOI: 10.1183/13993003.congress-2015.PA4903

Citation Manager Formats

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

Share
Balancing TGFbeta/BMP in pulmonary arterial hypertension
Nina Rol, Robert Szulcek, Marie-José Goumans, Chris Dickhoff, Anton Vonk-Noordegraaf, Harm Jan Bogaard, Geerten Van Nieuw Amerongen
European Respiratory Journal Sep 2015, 46 (suppl 59) PA4903; DOI: 10.1183/13993003.congress-2015.PA4903
Reddit logo Technorati logo Twitter logo Connotea logo Facebook logo Mendeley logo

Jump To

  • Article
  • Info & Metrics
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Effects of apoptosis signal- regulating kinase 1 (ASK1) inhibition in experimental pressure overload-induced right ventricular dysfunction
  • LSC Abstract – Glutamatergic signaling through pulmonary vascular NMDA receptors in pulmonary hypertension
  • CD163 is expressed and modulated in human pulmonary artery smooth muscle cells: Implications for pulmonary artery hypertension
Show more 4.3 Pulmonary Circulation and Pulmonary Vascular Disease

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • 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 © 2023 by the European Respiratory Society