Activation of farnesoid X receptor induces RECK expression in mouse liver

Abstract

Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor superfamily, and functions as a transcription factor regulating the transcription of numerous genes involved in bile acid homeostasis, lipoprotein and glucose metabolism. In the present study, we identified RECK, a membrane-anchored inhibitor of matrix metalloproteinases, as a novel target gene of FXR in mouse liver. We found that FXR agonist substantially augmented hepatic RECK mRNA and protein expression in vivo and in vitro. FXR regulated the transcription of RECK through directly binding to FXR response element located within intron 1 of the mouse RECK gene. Moreover, FXR agonist reversed the down-regulation of RECK in the livers from mice fed a methionine and choline deficient diet. In summary, our data suggest that RECK is a novel transcriptional target of FXR in mouse liver, and provide clues to better understanding the function of FXR in liver.

Keywords: FBS; FXR; Farnesoid X receptor; MCD; MMPs; PEPCK; Primary hepatocytes; RECK; RXRα; SHP; SREBP-1c; Transactivation; farnesoid X receptor; fetal bovine serum; matrix metalloproteinases; methionine and choline deficient; phosphoenolpyruvate carboxykinase; retinoid X receptor α; reversion-inducing cysteine rich protein with Kazal motifs; small heterodimer partner; sterol regulatory element-binding protein-1c.