Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices

Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays...

Full description

Bibliographic Details
Main Authors:	Oenema, Tjitske A., Maarsingh, Harm, Smit, Marieke, Groothuis, Geny M. M., Meurs, Herman, Gosens, Reinoud
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694103/

id	pubmed-3694103
recordtype	oai_dc
spelling	pubmed-36941032013-07-09 Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices Oenema, Tjitske A. Maarsingh, Harm Smit, Marieke Groothuis, Geny M. M. Meurs, Herman Gosens, Reinoud Research Article Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin) after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A) or TGF-β receptor kinase (SB431542) prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl) mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling. Public Library of Science 2013-06-26 /pmc/articles/PMC3694103/ /pubmed/23840342 http://dx.doi.org/10.1371/journal.pone.0065580 Text en © 2013 Oenema et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Oenema, Tjitske A. Maarsingh, Harm Smit, Marieke Groothuis, Geny M. M. Meurs, Herman Gosens, Reinoud
spellingShingle	Oenema, Tjitske A. Maarsingh, Harm Smit, Marieke Groothuis, Geny M. M. Meurs, Herman Gosens, Reinoud Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices
author_facet	Oenema, Tjitske A. Maarsingh, Harm Smit, Marieke Groothuis, Geny M. M. Meurs, Herman Gosens, Reinoud
author_sort	Oenema, Tjitske A.
title	Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices
title_short	Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices
title_full	Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices
title_fullStr	Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices
title_full_unstemmed	Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices
title_sort	bronchoconstriction induces tgf-β release and airway remodelling in guinea pig lung slices
description	Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin) after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A) or TGF-β receptor kinase (SB431542) prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl) mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694103/
_version_	1611989879686692864

Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices

Similar Items