title: Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix.
abstract: 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.
authors.affiliation: Respiratory Research Group, Department of Pharmacology, University of Sydney, Sydney, NSW, Australia 2006. janette@pharmacol.usyd.edu.au
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.forename: Qi
authors.initials: Q
authors.lastname: Ge
authors.forename: Maree H
authors.initials: MH
authors.lastname: Poniris
authors.forename: Sarah
authors.initials: S
authors.lastname: Boustany
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Twigg
authors.forename: Judith L
authors.initials: JL
authors.lastname: Black
authors.forename: Peter R A
authors.initials: PR
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D016022:Case-Control Studies; D003094:Collagen / Q000096:biosynthesis; D055513:Connective Tissue Growth Factor; D015232:Dinoprostone / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000494:pharmacology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C526317:CCN2 protein, human; D005353:Fibronectins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D015232:Dinoprostone