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Collagen remodelling by airway smooth muscle is resistant to steroids and β₂-agonists.
Eur Respir J. 2011 Jan; 37(1):173-82.ER

Abstract

Bi-directional interactions between airway smooth muscle (ASM) and the altered extracellular matrix (ECM) may influence airway wall remodelling and ASM function in asthma. We have investigated the capacity of cultured human ASM to reorganise the structure of three-dimensional collagen gels and the effects of endothelin (ET)-1 and agents used to treat asthma. Human ASM cells were cast in type I collagen gels. Reductions in gel area over 72 h were determined in the absence and presence of ET-1 and potential inhibitors, steroids and β₂-adrenoceptor agonists. Changes in gel wet weights and hydroxyproline content were measured and ASM gel morphology was examined by scanning electron microscopy. Cell density-dependent reductions in gel area were augmented by ET-1, mediated via ET(A) receptors. This process was not associated with ASM contraction or proliferation, but was consistent with ASM tractional remodelling and migration leading to collagen condensation rather than collagen degradation within gels. The collagen remodelling by ASM was unaffected by salbutamol and/or budesonide. This study demonstrates an additional potential role for ASM in ECM regulation and dysregulation in airways disease that is resistant to steroids and β₂-adrenoceptor agonists. Therapy-resistant collagen condensation within ASM bundles may facilitate ECM-ASM interactions and contribute to increased internal airways resistance.

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Authors+Show Affiliations

Bourke JE
Dept of Pharmacology, University of Melbourne, Victoria, Australia. janeew@unimelb.edu.au
Li X
No affiliation info available
Foster SR
No affiliation info available
Wee E
No affiliation info available
Dagher H
No affiliation info available
Ziogas J
No affiliation info available
Harris T
No affiliation info available
Bonacci JV
No affiliation info available
Stewart AG
No affiliation info available

MeSH

Adrenergic beta-AgonistsAsthmaBronchiCalciumCell LineCell MovementCollagenDrug ResistanceExtracellular MatrixGlucocorticoidsHumansHydroxyprolineMatrix Metalloproteinase 2Microscopy, Electron, ScanningModels, BiologicalMuscle, SmoothSteroids

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20595143

Citation

Bourke, J E., et al. "Collagen Remodelling By Airway Smooth Muscle Is Resistant to Steroids and Β₂-agonists." The European Respiratory Journal, vol. 37, no. 1, 2011, pp. 173-82.
Bourke JE, Li X, Foster SR, et al. Collagen remodelling by airway smooth muscle is resistant to steroids and β₂-agonists. Eur Respir J. 2011;37(1):173-82.
Bourke, J. E., Li, X., Foster, S. R., Wee, E., Dagher, H., Ziogas, J., Harris, T., Bonacci, J. V., & Stewart, A. G. (2011). Collagen remodelling by airway smooth muscle is resistant to steroids and β₂-agonists. The European Respiratory Journal, 37(1), 173-82. https://doi.org/10.1183/09031936.00008109
Bourke JE, et al. Collagen Remodelling By Airway Smooth Muscle Is Resistant to Steroids and Β₂-agonists. Eur Respir J. 2011;37(1):173-82. PubMed PMID: 20595143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Collagen remodelling by airway smooth muscle is resistant to steroids and β₂-agonists. AU - Bourke,J E, AU - Li,X, AU - Foster,S R, AU - Wee,E, AU - Dagher,H, AU - Ziogas,J, AU - Harris,T, AU - Bonacci,J V, AU - Stewart,A G, Y1 - 2010/07/01/ PY - 2010/7/3/entrez PY - 2010/7/3/pubmed PY - 2011/5/24/medline SP - 173 EP - 82 JF - The European respiratory journal JO - Eur Respir J VL - 37 IS - 1 N2 - Bi-directional interactions between airway smooth muscle (ASM) and the altered extracellular matrix (ECM) may influence airway wall remodelling and ASM function in asthma. We have investigated the capacity of cultured human ASM to reorganise the structure of three-dimensional collagen gels and the effects of endothelin (ET)-1 and agents used to treat asthma. Human ASM cells were cast in type I collagen gels. Reductions in gel area over 72 h were determined in the absence and presence of ET-1 and potential inhibitors, steroids and β₂-adrenoceptor agonists. Changes in gel wet weights and hydroxyproline content were measured and ASM gel morphology was examined by scanning electron microscopy. Cell density-dependent reductions in gel area were augmented by ET-1, mediated via ET(A) receptors. This process was not associated with ASM contraction or proliferation, but was consistent with ASM tractional remodelling and migration leading to collagen condensation rather than collagen degradation within gels. The collagen remodelling by ASM was unaffected by salbutamol and/or budesonide. This study demonstrates an additional potential role for ASM in ECM regulation and dysregulation in airways disease that is resistant to steroids and β₂-adrenoceptor agonists. Therapy-resistant collagen condensation within ASM bundles may facilitate ECM-ASM interactions and contribute to increased internal airways resistance. SN - 1399-3003 UR - https://www.unboundmedicine.com/medline/citation/20595143/Collagen_remodelling_by_airway_smooth_muscle_is_resistant_to_steroids_and_β₂_agonists_ L2 - http://erj.ersjournals.com/cgi/pmidlookup?view=long&pmid=20595143 DB - PRIME DP - Unbound Medicine ER -