Thrombomodulin (TM) serves as a vasoprotective molecule on the surface of 
vascular endothelial cells (VECs) to maintain the endothelial microenvironment 
by suppressing cellular proliferation, adhesion and inflammatory responses. 
Farnesoid X receptor (FXR), a nuclear receptor (NR) and originally considered as 
a bile acid-activated transcriptional factor, not only regulates metabolism 
homeostasis, but also influences cholesterol transport, vascular tension, and 
inflammation. Recent studies have shown that TM expression is upregulated by 
several NRs. However, it is unknown whether there is a link between FXR and TM. 
Our studies demonstrated that TM expression and activity were up-regulated by 
FXR activation in VECs. Reporter assays showed that FXR activation significantly 
enhanced the transcriptional activity of human TM gene promoter. Elecrophoretic 
mobility-shift and chromatin immunoprecipitation assays indicated that FXR 
induced TM expression by binding to a novel FXR-responsive element (FXRE), an 
inverted repeat DNA motif, IR8 (-503 AGGTCCtcccaaagTGCCCT-484) in the promoter 
region of TM gene. These results suggest that FXR may serve as a novel molecular 
target for manipulating TM expression and activity in VECs, which may be helpful 
for designing the therapeutic strategies to the treatment of associated diseases 
by targeting FXR/TM pathway.