The G-Protein-Coupled Bile Acid Receptor Gpbar1 (TGR5) Inhibits Gastric Inflammation Through Antagonizing NF-κB Signaling Pathway
| العنوان: | The G-Protein-Coupled Bile Acid Receptor Gpbar1 (TGR5) Inhibits Gastric Inflammation Through Antagonizing NF-κB Signaling Pathway |
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| المؤلفون: | Cong Guo, Wei-Dong Chen, Qiqi Zhang, Hui Qi, Wendong Huang, Yingjie Yu, Donna Yu, Yan-Dong Wang, Jia Su |
| المصدر: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 6 (2015) |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Pharmacology, lcsh:RM1-950, NF-κB, Inflammation, Biology, G protein-coupled bile acid receptor, Cell biology, IκBα, chemistry.chemical_compound, lcsh:Therapeutics. Pharmacology, Mediator, GPCR, chemistry, GPBAR1, Immunology, medicine, tgr5, Phosphorylation, Pharmacology (medical), Signal transduction, medicine.symptom, gastric inflammation, G protein-coupled receptor, Original Research |
| الوصف: | Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well-known for its roles in regulation of energy homeostasis and glucose metabolism. Here, we show that mice lacking TGR5 were much more susceptible to lipopolysaccharide (LPS)-induced acute gastric inflammation than wild-type (WT) mice and TGR5 is a negative regulator of gastric inflammation through antagonizing NF-κB signaling pathway. We found that the treatment of TGR5 ligands 23(S)-mCDCA and GPBARA (3-(2-Chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide) suppressed gene and protein expression mediated by NF-κB signaling. TGR5 overexpression with ligand treatment inhibited gene expression of interferon-inducible protein 10 (IP-10), TNF-α, and chemoattractant protein-1 (MCP-1) induced by LPS. Furthermore, we revealed that TGR5 activation antagonized NF-κB signaling pathway through suppressing its transcription activity, the phosphorylation of IκBα and p65 translocation, which suggests that TGR5 antagonizes gastric inflammation at least in part by inhibiting NF-κB signaling. These findings identify TGR5 as a negative mediator of gastric inflammation that may serve as an attractive therapeutic tool for human gastric inflammation and cancer. |
| تدمد: | 1663-9812 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b23c72aec2ac485dc7c7fa4329759d76 https://pubmed.ncbi.nlm.nih.gov/26696888 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b23c72aec2ac485dc7c7fa4329759d76 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16639812 |
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