ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Ciliary subcellular localization of TGR5 determines the cholangiocyte functional response to bile acid signaling.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 136 citations in OpenAlex.
- Primary cilia: sensors of biliary homeostasis and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 2026Review
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Targeting of a Bile Acid Receptor, Takeda G Protein Receptor 5 [TGR5], by a Novel First-in-Class Competitive Antagonist, SBI-364, Diminishes Hepatic and Renal Cystogenesis in Polycystic Liver and Kidney Disease.ACS pharmacology & translational science · 2025Article
- The Critical Role of the Bile Acid Receptor TGR5 in Energy Homeostasis: Insights into Physiology and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Biological Actions of Bile Acids via Cell Surface Receptors.International journal of molecular sciences · 2025Review
- AhR governs lipid metabolism: the role of gut microbiota.Frontiers in microbiology · 2025Review
- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
- Article
- Protective effect of UDCA against IL-11- induced cardiac fibrosis is mediated by TGR5 signalling.Frontiers in cardiovascular medicine · 2024Article
- Hepatic β-arrestins: potential roles in liver health and disease.Molecular biology reports · 2023Review
- Sequence of events leading to primary biliary cholangitis.World journal of gastroenterology · 2023Review
- Primary cilia as dynamic and diverse signalling hubs in development and disease.Nature reviews. Genetics · 2023Review
- Relevance of Bile Acids in Cholangiocarcinoma Pathogenesis: Critical Revision and Future Directions.Cells · 2023Review
- Bile acid-mediated signaling in cholestatic liver diseases.Cell & bioscience · 2023Review
- Bile Acids and Biliary Fibrosis.Cells · 2023Review
- Secondary bile acids and the biliary epithelia: The good and the bad.World journal of gastroenterology · 2023Review
- Human Placental Mesenchymal Stem Cells Relieve Primary Sclerosing Cholangitis via Upregulation of TGR5 in Mdr2Research (Washington, D.C.) · 2023Article
- Compartmentalised cAMP signalling in the primary cilium.Frontiers in physiology · 2023Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
TGR5, the G protein-coupled bile acid receptor that transmits bile acid signaling into a cell functional response via the intracellular cAMP signaling pathway, is expressed in human and rodent cholangiocytes. However, detailed information on the localization and function of cholangiocyte TGR5 is limited. We demonstrated that in human (H69 cells) and rat cholangiocytes, TGR5 is localized to multiple, diverse subcellular compartments, with its strongest expression on the apical plasma, ciliary, and nuclear membranes. To evaluate the relationship between ciliary TGR5 and the cholangiocyte functional response to bile acid signaling, we used a model of ciliated and nonciliated H69 cells and demonstrated that TGR5 agonists induce opposite changes in cAMP and ERK levels in cells with and without primary cilia. The cAMP level was increased in nonciliated cholangiocytes but decreased in ciliated cells. In contrast, ERK signaling was induced in ciliated cholangiocytes but suppressed in cells without cilia. TGR5 agonists inhibited proliferation of ciliated cholangiocytes but activated proliferation of nonciliated cells. The observed differential effects of TGR5 agonists were associated with the coupling of TGR5 to Gαi protein in ciliated cells and Gαs protein in nonciliated cholangiocytes. The functional responses of nonciliated and ciliated cholangiocytes to TGR5-mediated bile acid signaling may have important pathophysiological significance in cilia-related liver disorders (i.e., cholangiociliopathies), such as polycystic liver disease. In summary, TGR5 is expressed on diverse cholangiocyte compartments, including a primary cilium, and its ciliary localization determines the cholangiocyte functional response to bile acid signaling.
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