Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenals, and intestine. FXR may play an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. In this study, we report that FXR is also expressed in rat pulmonary artery endothelial cells (EC), a "nonclassical" bile acid target tissue. FXR is functional in EC, as demonstrated by induction of its target genes such as small heterodimer partner (SHP) after treatment with chenodeoxycholic acid, a FXR agonist. Interestingly, activation of FXR in EC led to downregulation of endothelin (ET)-1 expression. Reporter assays showed that activation of FXR inhibited transcriptional activation of the human ET-1 gene promoter and also repressed the activity of a heterologous promoter driven by activator protein (AP)-1 response elements. Electrophoretic mobility-shift and chromatin immunoprecipitation assays indicated that FXR reduced the binding activity of AP-1 transcriptional factors, suggesting that FXR may suppress ET-1 expression via negatively interfering with AP-1 signaling. These studies suggest that FXR may play a role in endothelial homeostasis and may serve as a novel molecular target for manipulating ET-1 expression in vascular EC.

He, Fengtian
Li, Jiang
Mu, Ying
Kuruba, Ramalinga
Ma, Zheng
Wilson, Annette
Alber, Sean
Jiang, Yu
Stevens, Troy
Watkins, Simon
Pitt, Bruce
Xie, Wen
Li, Song
Item Type: 
Journal Article
Publication Title: 
Circulation Research
Journal Abbreviation: 
Circ. Res.
Publication Date: 
Feb 3, 2006
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 16357303

Turabian/Chicago Citation

Fengtian He, Jiang Li, Ying Mu, Ramalinga Kuruba, Zheng Ma, Annette Wilson, Sean Alber, Yu Jiang, Troy Stevens, Simon Watkins, Bruce Pitt, Wen Xie and Song Li. Feb 3, 2006. "Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells." Circulation Research 98: 2: 192-199. 10.1161/01.RES.0000200400.55539.85.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1161/01.RES.0000200400.55539.85 | issn = 1524-4571 | volume = 98 | pages = 192-199 | last = He | first = Fengtian | coauthors = Li, Jiang, Mu, Ying, Kuruba, Ramalinga, Ma, Zheng, Wilson, Annette, Alber, Sean, Jiang, Yu, Stevens, Troy, Watkins, Simon, Pitt, Bruce, Xie, Wen, Li, Song | title = Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells | journal = Circulation Research | date = Feb 3, 2006 | pmid = | pmc = }} </ref>