Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP)
| Autor: | Billy K. C. Chow, Ian P. Y. Lam, Leo T. O. Lee, Gianfranco Alpini, Hueng-Sik Choi |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
animal structures Transcription Genetic Physiology medicine.drug_class Duodenum Enteroendocrine Cells Cholestyramine Resin Down-Regulation Receptors Cytoplasmic and Nuclear Nerve Tissue Proteins Secretin family Cholic Acid Biology Chenodeoxycholic Acid Transfection digestive system Cholangiocyte Secretin chemistry.chemical_compound Mice fluids and secretions Physiology (medical) Internal medicine Cell Line Tumor medicine Basic Helix-Loop-Helix Transcription Factors Benzene Derivatives Animals Humans RNA Messenger Promoter Regions Genetic Orphan receptor Binding Sites Hepatology Bile acid Gastroenterology Cholic acid Diet Mice Inbred C57BL Liver and Biliary Tract Endocrinology Gastrointestinal hormone chemistry embryonic structures Small heterodimer partner RNA Interference hormones hormone substitutes and hormone antagonists |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 297(1) |
| ISSN: | 1522-1547 |
| Popis: | Small heterodimer partner (SHP) is an orphan nuclear receptor in which gene expression can be upregulated by bile acids. It regulates its target genes by repressing the transcriptional activities of other nuclear receptors including NeuroD, which has been shown to regulate secretin gene expression. Here, we evaluated the regulation on duodenal secretin gene expression by SHP and selected bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA). In vitro treatment of CDCA or fexaramine elevated the SHP transcript level and occupancy on secretin promoter. The increase in the SHP level, induced by bile acid treatment or overexpression, reduced secretin gene expression, whereas this gene inhibitory effect was reversed by silencing of endogenous SHP. In in vivo studies, double-immunofluorescence staining demonstrated the coexpression of secretin and SHP in mouse duodenum. Feeding mice with 1% CA-enriched rodent chow resulted in upregulation of SHP and a concomitant decrease in secretin transcript and protein levels in duodenum compared with the control group fed with normal chow. A diet enriched with 5% cholestyramine led to a decrease in SHP level and a corresponding increase in secretin expression. Overall, this study showed that bile acids via SHP inhibit duodenal secretin gene expression. Because secretin is a key hormone that stimulates bile flow in cholangiocytes, this pathway thus provides a novel means to modulate secretin-stimulated choleresis in response to intraduodenal bile acids. |
| Databáze: | OpenAIRE |
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