Abstract
Transforming growth factor (TGF)-beta is a key cytokine in the pathogenesis of pulmonary fibrosis, and pharmacological interference with TGF-beta can ameliorate the fibrotic tissue response. The small proteoglycans decorin and biglycan are able to bind and inhibit TGF-beta activity in vitro. Although decorin has anti-TGF-beta properties in vivo, little is known about the physiological role of biglycan in vivo. Adenoviral gene transfer was used to overexpress active TGF-beta, decorin, and biglycan in cell culture and in murine lungs. Both proteoglycans were able to interfere with TGF-beta bioactivity in vitro in a dose-dependant manner. In vivo, overexpression of TGF-beta resulted in marked lung fibrosis, which was significantly reduced by concomitant overexpression of decorin. Biglycan, however, had no significant effect on lung fibrosis induced by TGF-beta. The data suggest that differences in tissue distribution are responsible for the different effects on TGF-beta bioactivity in vivo, indicating that decorin, but not biglycan, has potential therapeutic value in fibrotic disorders of the lung.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Animals
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Biglycan
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Bronchoalveolar Lavage Fluid / chemistry
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Bronchoalveolar Lavage Fluid / cytology
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Cell Line
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Decorin
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Dose-Response Relationship, Drug
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Extracellular Matrix Proteins
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Female
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Gene Transfer Techniques
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Genetic Vectors / genetics
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Genetic Vectors / metabolism
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Genetic Vectors / pharmacology
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Humans
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Hydroxyproline / metabolism
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Immunohistochemistry
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Lung / metabolism*
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Lung / pathology
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Mice
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Mice, Inbred C57BL
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Proteoglycans / genetics
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Proteoglycans / metabolism
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Proteoglycans / pharmacology*
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Pulmonary Fibrosis / chemically induced
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Pulmonary Fibrosis / metabolism
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Pulmonary Fibrosis / pathology
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Pulmonary Fibrosis / prevention & control*
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Tissue Distribution
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Transforming Growth Factor beta / antagonists & inhibitors*
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Transforming Growth Factor beta / biosynthesis
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Transforming Growth Factor beta / genetics
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Treatment Outcome
Substances
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BGN protein, human
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Bgn protein, mouse
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Biglycan
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DCN protein, human
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Dcn protein, mouse
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Decorin
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Extracellular Matrix Proteins
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Proteoglycans
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Transforming Growth Factor beta
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Hydroxyproline