Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage

• DOI: 10.1042/bj20102096
• Publication Date: 2011-07-04T15:47:31Z
• Authors: Fan Lian; Xiangbin Xing; Gang Yuan; Claus Schäfer; Sandra Rauser; Axel Walch; Christoph Röcken; Martin Ebeling; Matthew B. Wright; Roland M. Schmid; Matthias P. A. Ebert; Elke Burgermeister
• Keywords: Farnesoid X receptor; Chenodeoxycholic acid

Bile acids from duodenogastric reflux promote inflammation and increase the risk for gastro-oesophageal cancers. FXR (farnesoid X receptor/NR1H4) is a transcription factor regulated by bile such as CDCA (chenodeoxycholic acid). protects liver intestinal tract against acid overload; however, functional role in stomach has not been described. We detected expression normal human GC (gastric cancer). mRNA protein were also present cell lines MKN45 SNU5, but AGS line. Transfection of into cells protected TNFα (tumour necrosis α)-induced damage. identified K13 (keratin 13), an anti-apoptotic desmosomes, novel CDCA-regulated FXR-target gene. bound to conserved regulatory element proximal promoter. Gastric was increased FXR-dependent manner chow diet enriched with 1% (w/w) indomethacin (35 mg/kg body weight intraperitoneal) C57BL/6 mice. FXR-deficient mice more susceptible indomethacin-induced gastric ulceration than their WT (wild-type) littermates. These results suggest that increases resistance murine epithelial inflammation-mediated damage may thus participate development GC.