ArticleHepatology (Baltimore, Md.)2017
TGR5 contributes to hepatic cystogenesis in rodents with polycystic liver diseases through cyclic adenosine monophosphate/Gαs signaling.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 78 citations in OpenAlex.
- From Structure to Dynamics: Activation Mechanism of the G Protein-Coupled Bile Acid Receptor 1‑GACS omega · 2026Article
- A novel TGR5 agonist Sauchinone ameliorates IMQ induced murine psoriasis by regulating macrophage polarization.Journal of advanced research · 2026Article
- Research Progress on the Mechanism and Targeted Intervention of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1)-Mediated "Inflammation-Apoptosis-Metabolism-Microcirculation" Regulatory Network in Hepatitis B-Associated Liver Failure.Drug design, development and therapy · 2026Review
- Role of intestinal SCFAs homeostasis in the hepatoprotective effect of Clostridium butyricum in T2DM.NPJ biofilms and microbiomes · 2025Article
- 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
- [Pentosan polysulfate alleviates cyclophosphamide-induced interstitial cystitis/bladder pain syndrome in mice by modulating gut microbiota and bile acid metabolism].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling.Hepatology (Baltimore, Md.) · 2025Article
- Select microbial metabolites in the small intestinal lumen regulate vagal activity via receptor-mediated signaling.iScience · 2025Article
- Therapeutic potential of oleanolic acid in liver diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy.Nature metabolism · 2024Article
- Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets.Journal of animal science and biotechnology · 2024Article
- Proanthocyanidin B2 derived metabolites may be ligands for bile acid receptors S1PR2, PXR and CAR: anJournal of biomolecular structure & dynamics · 2024Article
- The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.mSystems · 2024Article
- Smooth muscle contractile responses to bile acids in mouse ileum require TGR5 but not ASBT.Frontiers in neurology · 2024Article
- Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.Biological research · 2023Article
- G protein-coupled bile acid receptor 1 reduced hepatic immune response and inhibited NFκB, PI3K/AKT, and PKC/P38 MAPK signaling pathway in hybrid grouper.Journal of animal science · 2023Article
- Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis.International journal of molecular sciences · 2022Article
- Genetics, pathobiology and therapeutic opportunities of polycystic liver disease.Nature reviews. Gastroenterology & hepatology · 2022Review
- Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.Seminars in immunopathology · 2022Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatic cystogenesis in polycystic liver disease is associated with increased levels of cyclic adenosine monophosphate (cAMP) in cholangiocytes lining liver cysts. Takeda G protein receptor 5 (TGR5), a G protein-coupled bile acid receptor, is linked to cAMP and expressed in cholangiocytes. Therefore, we hypothesized that TGR5 might contribute to disease progression. We examined expression of TGR5 and Gα proteins in cultured cholangiocytes and in livers of animal models and humans with polycystic liver disease. In vitro, we assessed cholangiocyte proliferation, cAMP levels, and cyst growth in response to (1) TGR5 agonists (taurolithocholic acid, oleanolic acid [OA], and two synthetic compounds), (2) a novel TGR5 antagonist (m-tolyl 5-chloro-2-[ethylsulfonyl] pyrimidine-4-carboxylate [SBI-115]), and (3) a combination of SBI-115 and pasireotide, a somatostatin receptor analogue. In vivo, we examined hepatic cystogenesis in OA-treated polycystic kidney rats and after genetic elimination of TGR5 in double mutant TGR5
conclusionTGR5 contributes to hepatic cystogenesis by increasing cAMP and enhancing cholangiocyte proliferation; our data suggest that a TGR5 antagonist alone or concurrently with somatostatin receptor agonists represents a potential therapeutic approach in polycystic liver disease. (Hepatology 2017;66:1197-1218).
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