TRANSFORMING GROWTH FACTOR-BETA(1), FACTOR-BETA(2), AND FACTOR-BETA(3) STIMULATE FIBROBLAST PROCOLLAGEN PRODUCTION IN-VITRO BUT ARE DIFFERENTIALLY EXPRESSED DURING BLEOMYCIN-INDUCED LUNG FIBROSIS

Transforming growth factor (TGF)-beta(1) may potentiate wound healing and fibrosis by stimulating fibroblast collagen deposition. TGF-beta(1 ) is implicated in the pathogenesis of pulmonary fibrosis, but the rol e of TGF-beta(2) and TGF-beta(3) remains unclear. We examined their ef fects on lung fibroblast procollagen metabolism in vitro and localized their gene expression during bleomycin-induced lung fibrosis using in situ hybridization with digoxigenin-labeled riboprobes. All three iso forms stimulated fibroblast procollagen production. TGF-beta(3) was th e most potent and also reduced procollagen degradation. In normal mous e lung, TGF-beta(1) and TGF-beta(3) mRNA transcripts were abundant in bronchiolar epithelium. After bleomycin, TGF-beta(1) gene expression w as maximally enhanced at 10 days, with the signal being predominant in macrophages. Signal was also enhanced in mesenchymal, pulmonary endot helia, and mesothelial cells. After 35 days, the pattern of TGF-beta(1 ) gene expression returned to that of control lung. TGF-beta(3) gene e xpression remained unchanged throughout compared with controls. TGF-be ta(2) mRNA was not detected with the antisense probe, but signal obtai ned with the sense probe suggests the presence of a naturally occurrin g antisense. This study demonstrates that TGF-beta(1), - beta(2), and - beta(3) all exert profibrotic effects in vitro. However, TGF-beta is oform gene expression is differentially controlled during experimental pulmonary fibrosis with TGF-beta(1) the predominant isoform expressed during pathogenesis.