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Am J Physiol Lung Cell Mol Physiol 290: L153-L161, 2006. First published August 12, 2005; doi:10.1152/ajplung.00287.2005
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Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix

Janette K. Burgess,1,2 Qi Ge,1 Maree H. Poniris,1 Sarah Boustany,2 Stephen M. Twigg,3,4 Judith L. Black,1,2 and Peter R. A. Johnson1,2

1Respiratory Research Group, Department of Pharmacology, University of Sydney; 2Woolcock Institute of Medical Research, 3Discipline of Medicine, University of Sydney; and 4Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia

Submitted 4 July 2005 ; accepted in final form 4 August 2005

Airway remodeling describes the structural changes that occur in the asthmatic airway that include airway smooth muscle hyperplasia, increases in vascularity due to angiogenesis, and thickening of the basement membrane. Our aim in this study was to examine the effect of transforming growth factor-{beta} on the release of connective tissue growth factor and vascular endothelial growth factor from human airway smooth muscle cells derived from asthmatic and nonasthmatic patients. In addition we studied the immunohistochemical localization of these cytokines in the extracellular matrix after stimulating bronchial rings with transforming growth factor-{beta}. Connective tissue growth factor and vascular endothelial growth factor were released from both cell types and colocalized in the surrounding extracellular matrix. Prostaglandin E2 inhibited the increase in connective tissue growth factor mRNA but augmented the release of vascular endothelial growth factor. Matrix metalloproteinase-2 decreased the amount of connective tissue growth factor and vascular endothelial growth factor, but not fibronectin deposited in the extracellular matrix. This report provides the first evidence that connective tissue growth factor may anchor vascular endothelial growth factor to the extracellular matrix and that this deposition is decreased by matrix metalloproteinase-2 and prostaglandin E2. This relationship has the potential to contribute to the changes that constitute airway remodeling, therefore providing a novel focus for therapeutic intervention in asthma.

transforming growth factor-{beta}; airway remodeling; matrix metalloproteinase; prostaglandin E2


Address for reprint requests and other correspondence: J. Burgess, Respiratory Research Group, Dept. of Pharmacology, Bosch Bldg., D05, Univ. of Sydney, Sydney, NSW, Australia 2006 (e-mail: janette{at}pharmacol.usyd.edu.au)




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