Bile acid regulates c-Jun expression through the orphan nuclear receptor SHP induction in gastric cells.
Bile reflux is considered to be one of the most important causative factors in gastric carcinogenesis, due to the attendant inflammatory changes in the gastric mucosa. In this study, we have assessed the molecular mechanisms inherent to the contribution of bile acid to the transcriptional regulation of inflammatory-related genes. In this study, we demonstrated that bile acid induced the expression of the SHP orphan nuclear receptor at the transcriptional level via c-Jun activation. Bile acid also enhanced the protein interaction of NF-kappaB and SHP, thereby resulting in an increase in c-Jun expression and the production of the inflammatory cytokine, TNFalpha. These results indicate that bile acid performs a critical function in the regulation of the induction of inflammatory-related genes in gastric cells, and that bile acid-mediated gene expression provides a pre-clue for the development of gastric cellular malformation.
Park
Won Il
WI
Bongseng Memorial Hospital, Dong Gu, Busan 601-723, Republic of Korea.
Park
Min Jung
MJ
An
Jin Kwang
JK
Choi
Yung Hyun
YH
Kim
Hye Young
HY
Cheong
Jaehun
J
Yang
Ung Suk
US
D001647:Bile Acids and Salts / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005756:Gastritis / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001647:Bile Acids and Salts; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D018160:Receptors, Cytoplasmic and Nuclear; D014409:Tumor Necrosis Factor-alpha; C099713:nuclear receptor subfamily 0, group B, member 2