Proteoglycans decorin and biglycan differentially modulate TGF-beta-mediated fibrotic responses in the lung

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 an d biglycan are able to bind and inhibit TGF-beta activity in vitro. Althoug h decorin has anti-TGF-beta properties in vivo, little is known about the p hysiological 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 bioac tivity in vitro in a dose-dependant manner. In vivo, overexpression of TGF- beta resulted in marked lung fibrosis, which was significantly reduced by c oncomitant overexpression of decorin. Biglycan, however, had no significant effect on lung fibrosis induced by TGF-beta. The data suggest that differe nces in tissue distribution are responsible for the different effects on TG F-beta bioactivity in vivo, indicating that decorin, but not biglycan, has potential therapeutic value in fibrotic disorders of the lung.