Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 290; no. 1; pp. L153 - L161
• Main Authors: Burgess, Janette K, Ge, Qi, Poniris, Maree H, Boustany, Sarah, Twigg, Stephen M, Black, Judith L, Johnson, Peter R. A
• Format: Journal Article
• Language: English
• Published: United States 01.01.2006
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Asthma - metabolism; Bronchi - metabolism; Case-Control Studies; Collagen - biosynthesis; Connective Tissue Growth Factor; Dinoprostone - pharmacology; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Female; Fibronectins - biosynthesis; Humans; Immediate-Early Proteins - antagonists & inhibitors; Immediate-Early Proteins - biosynthesis; Immediate-Early Proteins - metabolism; Immunoprecipitation; In Vitro Techniques; Intercellular Signaling Peptides and Proteins - biosynthesis; Intercellular Signaling Peptides and Proteins - metabolism; Male; Matrix Metalloproteinase 2 - pharmacology; Middle Aged; Muscle, Smooth - metabolism; Recombinant Proteins - pharmacology; Tissue Distribution; Transforming Growth Factor beta - pharmacology; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00287.2005

1 Respiratory Research Group, Department of Pharmacology, University of Sydney; 2 Woolcock Institute of Medical Research, 3 Discipline of Medicine, University of Sydney; and 4 Department 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- 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- . Connective tissue growth factor and vascular endothelial growth factor were released from both cell types and colocalized in the surrounding extracellular matrix. Prostaglandin E 2 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 E 2 . 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- ; airway remodeling; matrix metalloproteinase; prostaglandin E 2 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 )