REQUIREMENT OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) TYPE-II RECEPTOR FOR TGF-BETA-INDUCED PROLIFERATION AND GROWTH

Growth regulation of fibroblasts is important for lung development and repair of lung injury. In this study, we investigated the role of tra nsforming growth factor-beta (TGF-beta) type II receptor in the TGF-be ta-dependent proliferative response of lung fibroblasts. TGF-beta stim ulated the proliferation of adult lung fibroblasts at a low concentrat ion (1 ng/ml), but inhibited the growth of fetal lung fibroblasts in a dose-dependent fashion (0.1-10 ng/ml). Cross-linking and Northern ana lysis demonstrated that the two lung fibroblast cell lines expressed t he TGF-beta type I receptor (T beta RI) and type II receptor (T beta R II). We overexpressed in lung fibroblasts a truncated derivative of T beta RII that lacked the cytoplasmic serine/threonine kinase domain (T beta RII Delta K). T beta RII Delta K was a dominant-negative inhibit or of TGF-beta signal transduction blocking not only TGF-beta-induced mitogenic action upon adult lung fibroblasts but also TGF-beta-induced growth inhibition of fetal lung fibroblasts. The results indicate tha t the type II receptor is indispensable for mediating both the mitogen ic and antiproliferative effects of TGF-beta upon lung fibroblasts.