Expression of Caveolin-1 reduces cellular responses to TGF-β1 through down-regulating the expression of TGF-β type II receptor gene in NIH3T3 fibroblast cells

Transcriptional repression of Transforming Growth Factor-β type II receptor (TβRII) gene has been proposed to be one of the major mechanisms leading to TGF-β resistance. In this study, we demonstrate that expression of Caveolin-1 (Cav-1) gene in NIH3T3 fibroblast cells down-regulates the expression of TβRII gene in the transcriptional level, eventually resulting in the decreased responses to TGF-β. The reduced expression of TβRII gene by Cav-1 appeared to be due to the changes of the sequence-specific DNA binding proteins to either Positive Regulatory Element 1 (PRE1) or PRE2 of the TβRII promoter. In addition, Cav-1 expression inhibited TGF-β-mediated cellular proliferation and Plasminogen Activator Inhibitor (PAI)-1 gene expression as well as TGF-β-induced luciferase activity. Furthermore, the inhibition of endogeneous Cav-1 by small interfering RNA increased the expression of TβRII gene. These findings strongly suggest that expression of Cav-1 leads to the decreased cellular responsiveness to TGF-β through down-regulating TβRII gene expression.