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Mechanical strain causes adaptive change in bronchial fibroblasts enhancing profibrotic and inflammatory responses

Mechanical strain causes adaptive change in bronchial fibroblasts enhancing profibrotic and inflammatory responses
Mechanical strain causes adaptive change in bronchial fibroblasts enhancing profibrotic and inflammatory responses
Asthma is characterized by periodic episodes of bronchoconstriction and reversible airway obstruction; these symptoms are attributable to a number of factors including increased mass and reactivity of bronchial smooth muscle and extracellular matrix (ECM) in asthmatic airways. Literature has suggested changes in cell responses and signaling can be elicited via modulation of mechanical stress acting upon them, potentially affecting the microenvironment of the cell. In this study, we hypothesized that mechanical strain directly affects the (myo)fibroblast phenotype in asthma. Therefore, we characterized responses of bronchial fibroblasts, from 6 normal and 11 asthmatic non-smoking volunteers, exposed to cyclical mechanical strain using flexible silastic membranes. Samples were analyzed for proteoglycans, ?-smooth muscle actin (?SMA), collagens I and III, matrix metalloproteinase (MMP) 2 & 9 and interleukin-8 (IL-8) by qRT-PCR, Western blot, zymography and ELISA. Mechanical strain caused a decrease in ?SMA mRNA but no change in either ?SMA protein or proteoglycan expression. In contrast the inflammatory mediator IL-8, MMPs and interstitial collagens were increased at both the transcriptional and protein level. The results demonstrate an adaptive response of bronchial fibroblasts to mechanical strain, irrespective of donor. The adaptation involves cytoskeletal rearrangement, matrix remodelling and inflammatory cytokine release. These results suggest that mechanical strain could contribute to disease progression in asthma by promoting inflammation and remodelling responses.
1932-6203
1-16
Manuyakorn, Wiparat
ad62b7a2-bb60-4a33-b37d-c1be767915af
Smart, David
3468eafa-5280-40a1-9fda-1bdc07dd914f
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Haitchi, Hans
68dadb29-305d-4236-884f-e9c93f4d78fe
Holgate, Stephen
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Manuyakorn, Wiparat
ad62b7a2-bb60-4a33-b37d-c1be767915af
Smart, David
3468eafa-5280-40a1-9fda-1bdc07dd914f
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Haitchi, Hans
68dadb29-305d-4236-884f-e9c93f4d78fe
Holgate, Stephen
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Manuyakorn, Wiparat, Smart, David, Bucchieri, Fabio, Haitchi, Hans, Holgate, Stephen, Howarth, Peter and Davies, Donna (2016) Mechanical strain causes adaptive change in bronchial fibroblasts enhancing profibrotic and inflammatory responses. PLoS ONE, 11 (4), 1-16. (doi:10.1371/journal.pone.0153926). (PMID:27101406)

Record type: Article

Abstract

Asthma is characterized by periodic episodes of bronchoconstriction and reversible airway obstruction; these symptoms are attributable to a number of factors including increased mass and reactivity of bronchial smooth muscle and extracellular matrix (ECM) in asthmatic airways. Literature has suggested changes in cell responses and signaling can be elicited via modulation of mechanical stress acting upon them, potentially affecting the microenvironment of the cell. In this study, we hypothesized that mechanical strain directly affects the (myo)fibroblast phenotype in asthma. Therefore, we characterized responses of bronchial fibroblasts, from 6 normal and 11 asthmatic non-smoking volunteers, exposed to cyclical mechanical strain using flexible silastic membranes. Samples were analyzed for proteoglycans, ?-smooth muscle actin (?SMA), collagens I and III, matrix metalloproteinase (MMP) 2 & 9 and interleukin-8 (IL-8) by qRT-PCR, Western blot, zymography and ELISA. Mechanical strain caused a decrease in ?SMA mRNA but no change in either ?SMA protein or proteoglycan expression. In contrast the inflammatory mediator IL-8, MMPs and interstitial collagens were increased at both the transcriptional and protein level. The results demonstrate an adaptive response of bronchial fibroblasts to mechanical strain, irrespective of donor. The adaptation involves cytoskeletal rearrangement, matrix remodelling and inflammatory cytokine release. These results suggest that mechanical strain could contribute to disease progression in asthma by promoting inflammation and remodelling responses.

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Accepted/In Press date: 6 April 2016
e-pub ahead of print date: 21 April 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 393028
URI: https://eprints.soton.ac.uk/id/eprint/393028
ISSN: 1932-6203
PURE UUID: c4370294-a8ec-4f9f-9bfc-ee525c4fdb75
ORCID for Hans Haitchi: ORCID iD orcid.org/0000-0001-8603-302X
ORCID for Donna Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 06 May 2016 08:26
Last modified: 26 Nov 2019 02:08

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Contributors

Author: Wiparat Manuyakorn
Author: David Smart
Author: Fabio Bucchieri
Author: Hans Haitchi ORCID iD
Author: Stephen Holgate
Author: Peter Howarth
Author: Donna Davies ORCID iD

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