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Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells.

Xu Y, Watanabe T, Tanigawa T, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Arakawa T - J Clin Biochem Nutr (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of CDCA on the expression of Cdx2 and MUC2 in RGM-1 cells. RGM-1 cells treated with CDCA at doses ranging from 0 to 50 µM for 3 h or 6 h were subjected to measurement of expression level of mRNA for Cdx2 (A) or MUC2 (B) by real-time RT-PCR, respectively. n = 3, * p<0.01 compared with controls (vehicle-treated group). (C and D) Western blot analysis of Cdx2 (C) and MUC2 (D) in RGM-1 cells treated CDCA at doses ranging from 0 to 50 µM.
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Figure 1: Effect of CDCA on the expression of Cdx2 and MUC2 in RGM-1 cells. RGM-1 cells treated with CDCA at doses ranging from 0 to 50 µM for 3 h or 6 h were subjected to measurement of expression level of mRNA for Cdx2 (A) or MUC2 (B) by real-time RT-PCR, respectively. n = 3, * p<0.01 compared with controls (vehicle-treated group). (C and D) Western blot analysis of Cdx2 (C) and MUC2 (D) in RGM-1 cells treated CDCA at doses ranging from 0 to 50 µM.

Mentions: CDCA (0 to 50 µM) increased the expression level of Cdx2 and MUC2 mRNA in a dose-dependent fashion (Fig. 1A and B). Therefore, we used CDCA at a dose of 50 µM in this study. A dose-dependent upregulation of Cdx2 and MUC2 protein expression by CDCA was also observed as assessed by Western blotting (Fig. 1C and D).


Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells.

Xu Y, Watanabe T, Tanigawa T, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Arakawa T - J Clin Biochem Nutr (2009)

Effect of CDCA on the expression of Cdx2 and MUC2 in RGM-1 cells. RGM-1 cells treated with CDCA at doses ranging from 0 to 50 µM for 3 h or 6 h were subjected to measurement of expression level of mRNA for Cdx2 (A) or MUC2 (B) by real-time RT-PCR, respectively. n = 3, * p<0.01 compared with controls (vehicle-treated group). (C and D) Western blot analysis of Cdx2 (C) and MUC2 (D) in RGM-1 cells treated CDCA at doses ranging from 0 to 50 µM.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2803137&req=5

Figure 1: Effect of CDCA on the expression of Cdx2 and MUC2 in RGM-1 cells. RGM-1 cells treated with CDCA at doses ranging from 0 to 50 µM for 3 h or 6 h were subjected to measurement of expression level of mRNA for Cdx2 (A) or MUC2 (B) by real-time RT-PCR, respectively. n = 3, * p<0.01 compared with controls (vehicle-treated group). (C and D) Western blot analysis of Cdx2 (C) and MUC2 (D) in RGM-1 cells treated CDCA at doses ranging from 0 to 50 µM.
Mentions: CDCA (0 to 50 µM) increased the expression level of Cdx2 and MUC2 mRNA in a dose-dependent fashion (Fig. 1A and B). Therefore, we used CDCA at a dose of 50 µM in this study. A dose-dependent upregulation of Cdx2 and MUC2 protein expression by CDCA was also observed as assessed by Western blotting (Fig. 1C and D).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.

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.

No MeSH data available.


Related in: MedlinePlus