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Extracellular matrix proteins modulate asthmatic airway smooth muscle cell proliferation via an autocrine mechanism - 24/08/11

Doi : 10.1016/j.jaci.2003.12.312 
Peter R.A. Johnson, PhD a, c, , Janette K. Burgess, PhD a, c, P.Anne Underwood, PhD b, Wendy Au, BSc (Hons) a, Maree H. Poniris, BSc (Hons) a, Michael Tamm, MD a, d, Qi Ge, MSc a, Michael Roth, PhD a, c, d, Judith L. Black, MBBS a, c
From the aDepartment of Pharmacology, University of Sydney, Sydney, Australia; bCSIRO Molecular Science, Sydney, Australia; cWoolcock Institute of Medical Research, Royal Prince Alfred Hospital, Sydney, Australia; and the dDepartment of Internal Medicine, University of Basel, Basel, Switzerland 

Reprint requests: Dr P. R. A. Johnson, Department of Pharmacology, University of Sydney, NSW Australia 2006.

Sydney, Australia, and Basel, Switzerland

Abstract

Background

Airway remodeling is a key feature of persistent asthma and includes alterations in the extracellular matrix protein profile around the airway smooth muscle (ASM) and hyperplasia of the ASM. We have previously shown that nonasthmatic ASM cells in culture produce a range of extracellular matrix protein proteins and that asthmatic ASM cells proliferate faster than cells from nonasthmatic patients.

Objective

In this study, we compared the profile of extracellular matrix proteins produced by nonasthmatic and asthmatic ASM cells. We also examined the influence of these extracellular matrix protein proteins and conditioned medium derived from nonasthmatic or asthmatic ASM cells on the proliferation of nonasthmatic and asthmatic ASM cells.

Methods

Extracellular matrix proteins were measured by ELISA; proliferation of ASM cells was measured by tritiated thymidine incorporation.

Results

Production of perlecan and collagen I by the cells from asthmatic patients were significantly increased. In contrast, laminin ⍺1 and collagen IV were decreased. Chondroitin sulfate was detectable only in the cells from nonasthmatic patients. Compared with nonasthmatic extracellular matrix proteins, proteins from asthmatic cells enhanced ASM cell proliferation. Conditioned medium from asthmatic ASM cells did not induce greater proliferation compared with conditioned medium from nonasthmatic cells.

Conclusions

The data show that the profile of extracellular matrix protein components is altered in asthmatic cells and that this altered profile and not soluble mediators secreted from the ASM cells has the potential to influence the proliferation of these cells. These changes are likely to contribute to the airway wall remodeling that occurs in asthma.

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Keywords : Remodeling, airway smooth muscle proliferation, extracellular matrix, asthma

Abbreviations : ASM, CPM, DMEM, ECM, HASM, TdR


Esquema


 Supported by the NHMRC, Australia, and Astra Zeneca, Switzerland, and the Rebecca L. Cooper Foundation. Drs Johnson and Burgess contributed equally to this work.


© 2004  American Academy of Allergy, Asthma and Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 113 - N° 4

P. 690-696 - avril 2004 Regresar al número
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