title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032, China. Electronic address: meilingzhou2012@gmail.com.
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yhchloech@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D002713:Chlorine / Q000172:deficiency; D004032:Diet; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000172:deficiency; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D002713:Chlorine; D058851:GPI-Linked Proteins; D008715:Methionine; D018160:Receptors, Cytoplasmic and Nuclear; D025521:Tumor Suppressor Proteins; D000099150:Receptor, Farnesoid X-Activated; C529735:Reck protein, rat
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