Requirement of transforming growth factor-β (TGF-β) type II receptor for TGF-β-induced proliferation and growth inhibition

Abstract

Growth regulation of fibroblasts is important for lung development and repair of lung injury. In this study, we investigated the role of transforming growth factor-β (TGF-β) type II receptor in the TGF-β- dependent proliferative response of lung fibroblasts. TGF-β stimulated the proliferation of adult lung fibroblasts at a low concentration (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 analysis demonstrated that the two lung fibroblast cell lines expressed the TGF-β type I receptor (TβRI) and type II receptor (TβRII). We overexpressed in lung fibroblasts a truncated derivative of TβRII that lacked the cytoplasmic serine/threonine kinase domain (TβRIIΔK). TβRIIΔK was a dominant-negative inhibitor of TGF-β signal transduction blocking not only TGF-β-induced mitogenic action upon adult lung fibroblasts but also TGF-β-induced growth inhibition of fetal lung fibroblasts. The results indicate that the type II receptor is indispensable for mediating both the mitogenic and antiproliferative effects of TGF-β upon lung fibroblasts.