Abstract: Selenoprotein P (SeP) is a selenium-rich plasma protein which
accounts for more than 50% this study, the effect of
TGF-\beta_1 on the expression of SeP in the human liver cell
line HepG2 was investigated. Western analysis revealed a dose-dependent
reduction of SeP content in cell supernatant. RT-PCR analysis of SeP-mRNA
expression demonstrated a marked inhibition and a reporter gene under control
of the SeP promoter was negatively regulated by TGF-\beta_1.
Smad proteins are the transcriptional mediators of
TGF-β signaling. A putative Smad-binding element (SBE)
is present in the SeP promoter. In electrophoretic-mobility-shift assays,
TGF-\beta_1 enhanced the binding of nuclear proteins to this
SBE. Overexpression of Smad3 and 4 resulted in a downregulation of SeP-promoter
activity whereas deletion of the SBE led to a loss of
TGF-\beta_1 responsiveness. We conclude that SeP expression
is modulated by the binding of Smad3/4 complexes to a functional SBE in the SeP
promoter.
