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Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma.
Ann Allergy Asthma Immunol. 2009 Mar; 102(3):238-46.AA

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.

Authors+Show Affiliations

Department of Allergy and Immunology, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19354071

Citation

Royce, Simon G., et al. "Effect of Extracellular Matrix Composition On Airway Epithelial Cell and Fibroblast Structure: Implications for Airway Remodeling in Asthma." Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, vol. 102, no. 3, 2009, pp. 238-46.
Royce SG, Tan L, Koek AA, et al. Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma. Ann Allergy Asthma Immunol. 2009;102(3):238-46.
Royce, S. G., Tan, L., Koek, A. A., & Tang, M. L. (2009). Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma. Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, 102(3), 238-46. https://doi.org/10.1016/S1081-1206(10)60087-7
Royce SG, et al. Effect of Extracellular Matrix Composition On Airway Epithelial Cell and Fibroblast Structure: Implications for Airway Remodeling in Asthma. Ann Allergy Asthma Immunol. 2009;102(3):238-46. PubMed PMID: 19354071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of extracellular matrix composition on airway epithelial cell and fibroblast structure: implications for airway remodeling in asthma. AU - Royce,Simon G, AU - Tan,Liling, AU - Koek,Alicia A, AU - Tang,Mimi L K, PY - 2009/4/10/entrez PY - 2009/4/10/pubmed PY - 2009/4/25/medline SP - 238 EP - 46 JF - Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology JO - Ann Allergy Asthma Immunol VL - 102 IS - 3 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. SN - 1081-1206 UR - https://www.unboundmedicine.com/medline/citation/19354071/Effect_of_extracellular_matrix_composition_on_airway_epithelial_cell_and_fibroblast_structure:_implications_for_airway_remodeling_in_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1081-1206(10)60087-7 DB - PRIME DP - Unbound Medicine ER -