title: Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells.
abstract: Clinical and experimental studies showed that the reflux of bile into the stomach contributes to the induction of intestinal metaplasia of the stomach and gastric carcinogenesis. Caudal-type homeobox 2 (Cdx2) plays a key role in the exhibition of intestinal phenotypes by regulating the expression of intestine-specific genes such as goblet-specific gene mucin 2 (MUC2). We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (CDCA)-induced expression of Cdx2 and MUC2 in normal rat gastric epithelial cells (RGM-1 cells). RGM-1 cells were treated with CDCA or GW4064, an FXR agonist, in the presence or absence of guggulsterone, an FXR antagonist. CDCA induced dose-dependent expression of Cdx2 and MUC2 at both the mRNA and protein levels. The maximum stimulation of Cdx2 and MUC2 mRNA induced by CDCA was observed at 3 h and by 6 h, respectively. GW4064 also induced expression of these molecules. The effects of CDCA and GW4064 on expression of Cdx2 and MUC2 were abolished by guggulsterone. These findings suggest that bile acids may induce gastric intestinal metaplasia and carcinogenesis through the FXR.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Yingji
authors.initials: Y
authors.lastname: Xu
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Machida
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Oshitani
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa