Activation of FXR promotes intestinal metaplasia of gastric cells via SHP-dependent upregulation of the expression of CDX2

Oncology Letters
Haining ZhouYongquan Shi

Abstract

Gastric intestinal metaplasia (IM) induced by bile acid is a precancerous lesion of gastric adenocarcinoma and is associated with the expression of caudal-related homeobox 2 (CDX2). In the present study, the role of farnesoid X receptor (FXR) on the regulation of CDX2 in gastric cells was investigated and the underlying molecular mechanisms were examined. Human gastric cell lines were treated with chenodeoxycholic acid (CDCA) or FXR agonist GW4064. Cells were treated with CDCA in the presence or absence of the FXR antagonist or FXR siRNA transfection. Next, cells were treated with CDCA in the presence or absence of SHP siRNA transfection and FXR, CDX2 and SHP mRNA and protein levels were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. A chromatin immunoprecipitation assay was performed to examine the relationship between FXR and SHP and the expressions of FXR and CDX2 in gastritis and IM tissues were detected using immunohistochemistry. The results revealed that CDCA was able to induce CDX2 expression, which could be blocked by inhibition or knockdown of FXR. Mechanistically, FXR directly induced the expression of small heterodimer partner (SHP). SHP knockdown significantly ...Continue Reading

Methods Mentioned

BETA
transfection
Protein Assay
immunoprecipitation
PCR
ChIP

Software Mentioned

Quantity One
SPSS

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