Expression of Caveolin-1 reduces cellular responses to TGF-beta1 through down-regulating the expression of TGF-beta type II receptor gene in NIH3T3 fibroblast cells.
Transcriptional repression of Transforming Growth Factor-beta type II receptor (TbetaRII) gene has been proposed to be one of the major mechanisms leading to TGF-beta resistance. In this study, we demonstrate that expression of Caveolin-1 (Cav-1) gene in NIH3T3 fibroblast cells down-regulates the expression of TbetaRII gene in the transcriptional level, eventually resulting in the decreased responses to TGF-beta. The reduced expression of TbetaRII 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 TbetaRII promoter. In addition, Cav-1 expression inhibited TGF-beta-mediated cellular proliferation and Plasminogen Activator Inhibitor (PAI)-1 gene expression as well as TGF-beta-induced luciferase activity. Furthermore, the inhibition of endogeneous Cav-1 by small interfering RNA increased the expression of TbetaRII gene. These findings strongly suggest that expression of Cav-1 leads to the decreased cellular responsiveness to TGF-beta through down-regulating TbetaRII gene expression.
Lee
Eun Kyung
EK
Inha University College of Medicine, Incheon, Republic of Korea.
Lee
Youn Sook
YS
Han
In-Oc
IO
Park
Seok Hee
SH
D000818:Animals; D001667:Binding, Competitive; D051242:Caveolin 1 / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D051242:Caveolin 1; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II