Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma

Simon Guy Royce, Liling Tan, Alicia A Koek, Mimi LK Tang

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

BACKGROUND: Airway remodeling in asthma is characterized by structural changes to the airways including extracellular matrix (ECM) deposition and epithelial metaplasia. Extracellular matrix deposition in the subepithelial region may play an important role in modulation of epithelial cell and fibroblast structure and function because it lies in immediate contact with these cell types and exists within the functional epithelial mesenchymal trophic unit. OBJECTIVE: To investigate the effect of aberrant ECM components on airway epithelial cells and fibroblasts and the relationship among subepithelial ECM deposition, other remodeling changes, and airway hyperresponsiveness. METHODS: BEAS-2B human airway epithelial cells and WI-38 human airway fibroblast cells were cultured on various ECM protein substrates (Matrigel, representing normal basement membrane matrix, or aberrant matrix proteins collagen I, collagen III, and fibronectin). Airway remodeling changes were determined using morphometry in sections from a murine model of chronic allergic airway disease. Airway reactivity to methacholine was determined, and these parameters correlated. RESULTS: Abnormal ECM substrates induced epithelial and fibroblast proliferation and altered the cell morphology of both human airway epithelial cells and fibroblasts when compared with normal basement membrane ECM. Subepithelial matrix deposition in the mouse correlated with epithelial thickness, but only weak correlations were noted among the other parameters. CONCLUSIONS: We have demonstrated that ECM may affect the growth of airway epithelial cells and fibroblasts in vitro and may influence epithelial thickness in the mouse. These findings may have implications for understanding the pathogenesis of asthma and future therapeutic targeting of airway remodeling.
Original languageEnglish
Pages (from-to)238 - 246
Number of pages9
JournalAnnals of Allergy, Asthma and Immunology
Volume102
Issue number3
DOIs
Publication statusPublished - 2009
Externally publishedYes

Cite this

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title = "Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma",
abstract = "BACKGROUND: Airway remodeling in asthma is characterized by structural changes to the airways including extracellular matrix (ECM) deposition and epithelial metaplasia. Extracellular matrix deposition in the subepithelial region may play an important role in modulation of epithelial cell and fibroblast structure and function because it lies in immediate contact with these cell types and exists within the functional epithelial mesenchymal trophic unit. OBJECTIVE: To investigate the effect of aberrant ECM components on airway epithelial cells and fibroblasts and the relationship among subepithelial ECM deposition, other remodeling changes, and airway hyperresponsiveness. METHODS: BEAS-2B human airway epithelial cells and WI-38 human airway fibroblast cells were cultured on various ECM protein substrates (Matrigel, representing normal basement membrane matrix, or aberrant matrix proteins collagen I, collagen III, and fibronectin). Airway remodeling changes were determined using morphometry in sections from a murine model of chronic allergic airway disease. Airway reactivity to methacholine was determined, and these parameters correlated. RESULTS: Abnormal ECM substrates induced epithelial and fibroblast proliferation and altered the cell morphology of both human airway epithelial cells and fibroblasts when compared with normal basement membrane ECM. Subepithelial matrix deposition in the mouse correlated with epithelial thickness, but only weak correlations were noted among the other parameters. CONCLUSIONS: We have demonstrated that ECM may affect the growth of airway epithelial cells and fibroblasts in vitro and may influence epithelial thickness in the mouse. These findings may have implications for understanding the pathogenesis of asthma and future therapeutic targeting of airway remodeling.",
author = "Royce, {Simon Guy} and Liling Tan and Koek, {Alicia A} and Tang, {Mimi LK}",
year = "2009",
doi = "10.1016/S1081-1206(10)60087-7",
language = "English",
volume = "102",
pages = "238 -- 246",
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}

Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma. / Royce, Simon Guy; Tan, Liling; Koek, Alicia A; Tang, Mimi LK.

In: Annals of Allergy, Asthma and Immunology, Vol. 102, No. 3, 2009, p. 238 - 246.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma

AU - Royce, Simon Guy

AU - Tan, Liling

AU - Koek, Alicia A

AU - Tang, Mimi LK

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Airway remodeling in asthma is characterized by structural changes to the airways including extracellular matrix (ECM) deposition and epithelial metaplasia. Extracellular matrix deposition in the subepithelial region may play an important role in modulation of epithelial cell and fibroblast structure and function because it lies in immediate contact with these cell types and exists within the functional epithelial mesenchymal trophic unit. OBJECTIVE: To investigate the effect of aberrant ECM components on airway epithelial cells and fibroblasts and the relationship among subepithelial ECM deposition, other remodeling changes, and airway hyperresponsiveness. METHODS: BEAS-2B human airway epithelial cells and WI-38 human airway fibroblast cells were cultured on various ECM protein substrates (Matrigel, representing normal basement membrane matrix, or aberrant matrix proteins collagen I, collagen III, and fibronectin). Airway remodeling changes were determined using morphometry in sections from a murine model of chronic allergic airway disease. Airway reactivity to methacholine was determined, and these parameters correlated. RESULTS: Abnormal ECM substrates induced epithelial and fibroblast proliferation and altered the cell morphology of both human airway epithelial cells and fibroblasts when compared with normal basement membrane ECM. Subepithelial matrix deposition in the mouse correlated with epithelial thickness, but only weak correlations were noted among the other parameters. CONCLUSIONS: We have demonstrated that ECM may affect the growth of airway epithelial cells and fibroblasts in vitro and may influence epithelial thickness in the mouse. These findings may have implications for understanding the pathogenesis of asthma and future therapeutic targeting of airway remodeling.

AB - BACKGROUND: Airway remodeling in asthma is characterized by structural changes to the airways including extracellular matrix (ECM) deposition and epithelial metaplasia. Extracellular matrix deposition in the subepithelial region may play an important role in modulation of epithelial cell and fibroblast structure and function because it lies in immediate contact with these cell types and exists within the functional epithelial mesenchymal trophic unit. OBJECTIVE: To investigate the effect of aberrant ECM components on airway epithelial cells and fibroblasts and the relationship among subepithelial ECM deposition, other remodeling changes, and airway hyperresponsiveness. METHODS: BEAS-2B human airway epithelial cells and WI-38 human airway fibroblast cells were cultured on various ECM protein substrates (Matrigel, representing normal basement membrane matrix, or aberrant matrix proteins collagen I, collagen III, and fibronectin). Airway remodeling changes were determined using morphometry in sections from a murine model of chronic allergic airway disease. Airway reactivity to methacholine was determined, and these parameters correlated. RESULTS: Abnormal ECM substrates induced epithelial and fibroblast proliferation and altered the cell morphology of both human airway epithelial cells and fibroblasts when compared with normal basement membrane ECM. Subepithelial matrix deposition in the mouse correlated with epithelial thickness, but only weak correlations were noted among the other parameters. CONCLUSIONS: We have demonstrated that ECM may affect the growth of airway epithelial cells and fibroblasts in vitro and may influence epithelial thickness in the mouse. These findings may have implications for understanding the pathogenesis of asthma and future therapeutic targeting of airway remodeling.

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