Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistance

Jean‐Didier Breton; Déborah Heydet; Lora M. Starrs; Tim Veldre; Reena Ghildyal

doi:10.14814/phy2.13669

Back

Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistance

Journal article

Open access

Peer reviewed

Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistance

Jean‐Didier Breton, Déborah Heydet, Lora M. Starrs, Tim Veldre and Reena Ghildyal

Physiological reports, Vol.6(7), pp.1-12

13/04/2018

DOI: https://doi.org/10.14814/phy2.13669

PMCID: PMC5899214

PMID: 29654633

Files and links (2)

pdf

Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistance1.14 MBDownload View

Published (Version of record)CC BY V4.0, Open Access

url

Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistanceView

Published (Version of record)CC BY V4.0, Open

Metrics

139 File views/ downloads

7 Record Views

30 Times Cited - Web of Science

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Abstract

Airway remodeling

glucocorticoid resistance

Immunology

Lung

myofibroblast

Original Research

Respiratory Conditions Disorder and Diseases

Signalling Pathways

TGF β

transdifferentiation

Airway remodeling is an important process in response to repetitive inflammatory-mediated airway wall injuries. This is characterized by profound changes and reorganizations at the cellular and molecular levels of the lung tissue. It is of particular importance to understand the mechanisms involved in airway remodeling, as this is strongly associated with severe asthma leading to devastating airway dysfunction. In this study, we have investigated the transforming growth factor-β (TGFβ, a proinflammatory mediator)-activated fibroblast to myofibroblast transdifferentiation pathway, which plays a key role in asthma-related airway remodeling. We show that TGFβ induces fibroblast to myofibroblast transdifferentiation by the expression of αSMA, a specific myofibroblast marker. Furthermore, Smad2/Smad3 gene and protein expression patterns are different between fibroblasts and myofibroblasts. Such a change in expression patterns reveals an important role of these proteins in the cellular phenotype as well as their regulation by TGFβ during cellular transdifferentiation. Interestingly, our data show a myofibroblastic TGFβ-mediated increase in glucocorticoid receptor (GR) expression and a preferential localization of GR in the nucleus, compared to in fibroblasts. Furthermore, the GRβ (nonfunctional GR isoform) is increased relative to GRα (functional isoform) in myofibroblasts. These results are interesting as they support the idea of a GRβ-mediated glucocorticoid resistance observed in the severe asthmatic population. All together, we provide evidence that key players are involved in the TGFβ-mediated fibroblast to myofibroblast transdifferentiation pathway in a human lung fibroblast cell line. These players could be the targets of new treatments to limit airway remodeling and reverse glucocorticoid resistance in severe asthma.

Details

Title: Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistance
Creators: Jean‐Didier Breton - Present address
Déborah Heydet - University of Canberra
Lora M. Starrs - University of Canberra
Tim Veldre - University of Canberra
Reena Ghildyal - University of Canberra
Publication Details: Physiological reports, Vol.6(7), pp.1-12
Publisher: John Wiley and Sons Inc
Grant note: Centre for Research in Therapeutic Solutions University of Canberra Strategic Research Funds
Identifiers: 991013036341202368
Copyright: 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Academic Unit: National Centre for Naturopathic Medicine
Language: English
Resource Type: Journal article

Molecular changes during TGF β‐mediated lung fibroblast‐myofibroblast differentiation: implication for glucocorticoid resistance

Files and links (2)

Metrics

UN Sustainable Development Goals (SDGs)

Abstract

Details

Southern Cross University Social media