Bile Acid-Activated Receptors: GPBAR1 (TGR5) and Other G Protein-Coupled Receptors

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TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis

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Endogenous Bile Acids Are Ligands for the Nuclear Receptor FXR/BAR

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A G Protein-coupled Receptor Responsive to Bile Acids

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The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity

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Targeting hepatic macrophages to treat liver diseases

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Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate

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Identification of membrane-type receptor for bile acids (M-BAR)

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Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease

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Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome

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An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids

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Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel

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TGR5 Activation Inhibits Atherosclerosis by Reducing Macrophage Inflammation and Lipid Loading

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Primary sclerosing cholangitis

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Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas

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An update on the biology of sphingosine 1-phosphate receptors

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Risk Factors for Intrahepatic and Extrahepatic Cholangiocarcinoma in the United States: A Population-Based Case-Control Study

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The G-Protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) in mice

Wang, Y., Chen, W., Yu, D. D., FORMAN, B. M., & Huang, W. (2011) · Hepatology · doi:10.1002/hep.24525 · Cited by 488 · see citing works

The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation

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Expression and function of the bile acid receptor TGR5 in Kupffer cells

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Primary Sclerosing Cholangitis

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The TGR5 receptor mediates bile acid–induced itch and analgesia

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The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice

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The Biliary HCO3 − Umbrella: A Unifying Hypothesis on Pathogenetic and Therapeutic Aspects of Fibrosing Cholangiopathies

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Induction of Vascular Permeability by the Sphingosine-1-Phosphate Receptor–2 (S1P2R) and its Downstream Effectors ROCK and PTEN

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The Bile Acid Receptor GPBAR1 Regulates the M1/M2 Phenotype of Intestinal Macrophages and Activation of GPBAR1 Rescues Mice from Murine Colitis

Biagioli, M., Carino, A., Cipriani, S., Francisci, D., Marchianò, S., Scarpelli, P., Sorcini, D., Zampella, A., & Fiorucci, S. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700183 · Cited by 327 · see citing works

Conjugated Bile Acids Activate the Sphingosine–1–Phosphate Receptor 2 in Primary Rodent Hepatocytes

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A biliary HCO3- umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes

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Mouse Models of Nonalcoholic Steatohepatitis: Toward Optimization of Their Relevance to Human Nonalcoholic Steatohepatitis

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Vascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions

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Vascular endothelial dysfunction in cirrhosis

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The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells

Keitel, V., Reinehr, R., Gatsios, P., Rupprecht, C., Görg, B., Selbach, O., Häussinger, D., & Kubitz, R. (2007) · Hepatology · doi:10.1002/hep.21458 · Cited by 308 · see citing works

Novel Potent and Selective Bile Acid Derivatives as TGR5 Agonists: Biological Screening, Structure−Activity Relationships, and Molecular Modeling Studies

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Links Between Hepatic Fibrosis, Ductular Reaction, and Progenitor Cell Expansion

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The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders #

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Bile acids are nutrient signaling hormones

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Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice

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Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation

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The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain

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Selective Loss of Sphingosine 1-Phosphate Signaling with No Obvious Phenotypic Abnormality in Mice Lacking Its G Protein-coupled Receptor, LPB3/EDG-3

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TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue

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The G Protein-Coupled Bile Acid Receptor, TGR5, Stimulates Gallbladder Filling

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The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells

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Sphingosine-1-Phosphate Induces an Antiinflammatory Phenotype in Macrophages

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The role of sphingosine 1‐phosphate receptor 2 in bile‐acid–induced cholangiocyte proliferation and cholestasis‐induced liver injury in mice

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Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules

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Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system

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Bile Acid Receptor Activation Modulates Hepatic Monocyte Activity and Improves Nonalcoholic Fatty Liver Disease

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The Bile Acid Receptor TGR5 Activates the TRPA1 Channel to Induce Itch in Mice

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Sustained IL-6/STAT-3 Signaling in Cholangiocarcinoma Cells Due to SOCS-3 Epigenetic Silencing

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Bile salts mediate hepatocyte apoptosis by increasing cell surface trafficking of Fas

Sodeman, T. C., Bronk, S. F., Roberts, P. J., Miyoshi, H., & Gores, G. J. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.278.6.g992 · Cited by 215 · see citing works

Conjugated bile acid–activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression

Nagahashi, M., Takabe, K., Liu, R., Peng, K., Wang, X., Wang, Y., Hait, N. C., Wang, X., Allegood, J. C., Yamada, A., et al. (2014) · Hepatology · doi:10.1002/hep.27592 · Cited by 211 · see citing works

G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes

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TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro

Reich, M., Deutschmann, K., Sommerfeld, A., Klindt, C., Kluge, S., Kubitz, R., Ullmer, C., Knoefel, W. T., Herebian, D. A., Mayatepek, E., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309458 · Cited by 210 · see citing works

TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation.

Perino, A., Pols, T. W., Nomura, M., Stein, S., Pellicciari, R., & Schoonjans, K. (2014) · Journal of Clinical Investigation · doi:10.1172/jci76289 · Cited by 209 · see citing works

Inhibition of interleukin 6-mediated mitogen-activated protein kinase activation attenuates growth of a cholangiocarcinoma cell line

Park, J., Tadlock, L., Gores, G. J., & Patel, T. C. (1999) · Hepatology · doi:10.1002/hep.510300522 · Cited by 206 · see citing works

The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice

Péan, N., Doignon, I., Garcin, I., Besnard, A., Julien, B., Liu, B., Branchereau, S., Spraul, A., Guettier, C., Humbert, L., et al. (2013) · Hepatology · doi:10.1002/hep.26463 · Cited by 193 · see citing works

Deafness and Stria Vascularis Defects in S1P2 Receptor-null Mice

Kono, M., Belyantseva, I. A., Skoura, A., Frolenkov, G. I., Starost, M. F., Dreier, J. L., Lidington, D., Bolz, S., Friedman, T. B., Hla, T., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700370200 · Cited by 191 · see citing works

An essential role for the H218/AGR16/Edg‐5/LPB2 sphingosine 1‐phosphate receptor in neuronal excitability

MacLennan, A. J., Carney, P. R., Zhu, W., Chaves, A. H., Garcia, J., Grimes, J. R., Anderson, K. J., Roper, S. N., & Lee, N. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01634.x · Cited by 187 · see citing works

Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2

Liu, R., Zhao, R., Zhou, X., Liang, X., Campbell, D. J. W., Zhang, X., Zhang, L., Shi, R., Wang, G., Pandak, W. M., et al. (2014) · Hepatology · doi:10.1002/hep.27085 · Cited by 183 · see citing works

Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation

Zhang, G., Yang, L., Kim, G. S., Ryan, K. P., Lu, S., O’Donnell, R. K., Spokes, K., Shapiro, N. I., Aird, W. C., Kluk, M., et al. (2013) · Blood · doi:10.1182/blood-2012-11-467191 · Cited by 176 · see citing works

Bile acids PKA-dependently induce a switch of the IL-10/IL-12 ratio and reduce proinflammatory capability of human macrophages

Haselow, K., Bode, J. G., Wammers, M., Ehlting, C., Keitel, V., Kleinebrecht, L., Schupp, A.-K., Häussinger, D., & Graf, D. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0812396 · Cited by 164 · see citing works

Bile acids induce monocyte differentiation toward interleukin‐12 hypo‐producing dendritic cells via a TGR5‐dependent pathway

Ichikawa, R., Takayama, T., Yoneno∥, K., Kamada, N., Kitazume, M. T., Higuchi, H., Matsuoka, K., 渡辺, 光., Itoh, H., Kanai∥, T., et al. (2012) · Immunology · doi:10.1111/j.1365-2567.2012.03554.x · Cited by 163 · see citing works

Bile Salt–Induced Apoptosis Involves NADPH Oxidase Isoform Activation

Reinehr, R., Becker, S., Keitel, V., Eberle, A., Grether‐Beck, S., & Häussinger, D. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.09.023 · Cited by 149 · see citing works

Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism

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G‐protein‐coupled bile acid receptor plays a key role in bile acid metabolism and fasting‐induced hepatic steatosis in mice

Donepudi, A. C., Boehme, S., Li, F., & Chiang, J. Y. L. (2016) · Hepatology · doi:10.1002/hep.28707 · Cited by 147 · see citing works

Bile Acid-Induced Arrhythmia Is Mediated by Muscarinic M2 Receptors in Neonatal Rat Cardiomyocytes

Kadir, S. H. S. A., Miragoli, M., Abu‐Hayyeh, S., Moshkov, A. V., Xie, Q., Keitel, V., Nikolaev, V. O., Williamson, C., & Gorelik, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009689 · Cited by 144 · see citing works

Ciliary subcellular localization of TGR5 determines the cholangiocyte functional response to bile acid signaling

Masyuk, A. I., Huang, B. Q., Radtke, B. N., Gajdos, G. B., Splinter, P. L., Masyuk, T. V., Gradilone, S. A., & LaRusso, N. F. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00383.2012 · Cited by 143 · see citing works

TGR5 and Immunometabolism: Insights from Physiology and Pharmacology.

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Bile acid receptors in the biliary tree: TGR5 in physiology and disease

Deutschmann, K., Reich, M., Klindt, C., Dröge, C., Spomer, L., Häussinger, D., & Keitel, V. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.08.021 · Cited by 140 · see citing works

Bile salt—induced hepatocyte apoptosis involves epidermal growth factor receptor-dependent CD95 tyrosine phosphorylation

Reinehr, R., Graf, D., & Häussinger, D. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)01055-2 · Cited by 130 · see citing works

Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATPchannels

Lavoie, B. A., Balemba, O. B., Godfrey, C. B., Watson, C. A., Vassileva, G., Corvera, C. U., Nelson, M. T., & Mawe, G. M. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.192146 · Cited by 130 · see citing works

The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes

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Mutational Characterization of the Bile Acid Receptor TGR5 in Primary Sclerosing Cholangitis

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A Mouse Model of Cholestasis-Associated Cholangiocarcinoma and Transcription Factors Involved in Progression

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Sphingosine 1-phosphate (S1P)/S1P receptors are involved in human liver fibrosis by action on hepatic myofibroblasts motility

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Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2

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Perspective: TGR5 (Gpbar-1) in liver physiology and disease

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Role of a novel bile acid receptor TGR5 in the development of oesophageal adenocarcinoma

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Endocrine and paracrine role of bile acids

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Sphingosine-1-phosphate receptor 2

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Agonist-induced Coordinated Trafficking of Functionally Related Transport Proteins for Water and Ions in Cholangiocytes

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The roles of bile acids and sphingosine-1-phosphate signaling in the hepatobiliary diseases

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Bile Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Promotes Neuroinflammation during Hepatic Encephalopathy in Mice

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Mechanism of Vitamin D Receptor Inhibition of Cholesterol 7α-Hydroxylase Gene Transcription in Human Hepatocytes

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Role of TGR5 (GPBAR1) in Liver Disease

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FXR and TGR5 Agonists Ameliorate Liver Injury, Steatosis, and Inflammation After Binge or Prolonged Alcohol Feeding in Mice

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Involvement of integrins and Src in tauroursodeoxycholate-induced and swelling-induced choleresis

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Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice

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Taurolithocholic acid-3 sulfate induces CD95 trafficking and apoptosis in a c-Jun N-terminal kinase–dependent manner

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Bile‐Derived Organoids From Patients With Primary Sclerosing Cholangitis Recapitulate Their Inflammatory Immune Profile

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G-Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5) Agonists Reduce the Production of Proinflammatory Cytokines and Stabilize the Alternative Macrophage Phenotype

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Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line

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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

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Discovery of Intestinal Targeted TGR5 Agonists for the Treatment of Type 2 Diabetes

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Involvement of the Src family kinase yes in bile salt-induced apoptosis

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Design, Synthesis, and Antidiabetic Activity of 4-Phenoxynicotinamide and 4-Phenoxypyrimidine-5-carboxamide Derivatives as Potent and Orally Efficacious TGR5 Agonists

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Sphingosine 1-Phosphate Receptor 2 and 3 Mediate Bone Marrow-Derived Monocyte/Macrophage Motility in Cholestatic Liver Injury in Mice

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Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway

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Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice

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Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma

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Novel Small Molecule Agonist of TGR5 Possesses Anti-Diabetic Effects but Causes Gallbladder Filling in Mice

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Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression

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α5β1-integrins are sensors for tauroursodeoxycholic acid in hepatocytes

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TGR5 contributes to hepatic cystogenesis in rodents with polycystic liver diseases through cyclic adenosine monophosphate/Gαs signaling

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INT-767 improves histopathological features in a diet-induced ob/ob mouse model of biopsy-confirmed non-alcoholic steatohepatitis

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Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues

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Selective interaction of bile acids with muscarinic receptors: a case of molecular mimicry

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Forskolin-induced apical membrane insertion of virally expressed, epitope-tagged CFTR in polarized MDCK cells

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Reversal of Endothelial Dysfunction by GPBAR1 Agonism in Portal Hypertension Involves a AKT/FOXOA1 Dependent Regulation of H2S Generation and Endothelin-1

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Essential roles of sphingosine 1‐phosphate receptor types 1 and 3 in human hepatic stellate cells motility and activation

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Characterization of chenodeoxycholic acid as an endogenous antagonist of the G-coupled formyl peptide receptors

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Sphingosine 1-Phosphate (S1P)/S1P Receptor2/3 Axis Promotes Inflammatory M1 Polarization of Bone Marrow-Derived Monocyte/Macrophage via G(α)i/o/PI3K/JNK Pathway

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Cystathionine γ-lyase, a H2S-generating enzyme, is a GPBAR1-regulated gene and contributes to vasodilation caused by secondary bile acids

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Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2–Mediated Water Homeostasis

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Sphingosine 1-phosphate Receptor 2 Signaling Suppresses Macrophage Phagocytosis and Impairs Host Defense against Sepsis

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Bile acids induce hepatic differentiation of mesenchymal stem cells

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Decoding the vasoregulatory activities of bile acid-activated receptors in systemic and portal circulation: role of gaseous mediators

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Agonism for the bile acid receptor GPBAR1 reverses liver and vascular damage in a mouse model of steatohepatitis

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The bile acid receptor, TGR 5, regulates basal and cholinergic‐induced secretory responses in rat colon

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Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human

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TGR5: Pathogenetic Role and/or Therapeutic Target in Fibrosing Cholangitis?

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TGR5 in the Biliary Tree

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Bile acid receptor agonists INT747 and INT777 decrease oestrogen deficiency-related postmenopausal obesity and hepatic steatosis in mice

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Hydrophobic Bile Salts Induce Hepatocyte Shrinkage via NADPH Oxidase Activation

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Role of the G Protein-Coupled Bile Acid Receptor TGR5 in Liver Damage

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Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

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Antagonism of sphingosine 1-phosphate receptor 2 causes a selective reduction of portal vein pressure in bile duct-ligated rodents

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Sphingosine-1 phosphate promotes intestinal epithelial cell proliferation via S1PR2

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Deoxycholic Acid Conjugates Are Muscarinic Cholinergic Receptor Antagonists

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Lithocholylcholine, a Bile Acid/Acetylcholine Hybrid, Is a Muscarinic Receptor Antagonist

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Phosphatidylinositol-3-kinase p110γ contributes to bile salt-induced apoptosis in primary rat hepatocytes and human hepatoma cells

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TGR5 in cholangiocytes

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Ammonia Attenuates LPS-Induced Upregulation of Pro-Inflammatory Cytokine mRNA in Co-Cultured Astrocytes and Microglia

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2‐Phenoxy‐nicotinamides are Potent Agonists at the Bile Acid Receptor GPBAR1 (TGR5)

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Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)

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TGR5 Sequence Variation in Primary Sclerosing Cholangitis

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The Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Axis in Intestinal Epithelial Cells Regulates Intestinal Barrier Function During Intestinal Epithelial Cells–CD4+T-Cell Interactions

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S1P2 receptor mediates sphingosine-1-phosphate-induced fibronectin expression via MAPK signaling pathway in mesangial cells under high glucose condition

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Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR‐S1PR2 ‐dependent mechanism

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TGR5 in the Cholangiociliopathies

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Regulation of endothelin-A receptor sensitivity by cyclic adenosine monophosphate in rat hepatic stellate cells

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Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

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Cholangiocarcinoma development: The resurgence of bile acids

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Hepatobiliary Transport in Health and Disease

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5 Bile acid signaling in the liver and the biliary tree

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Dual role of the bile acid receptor Takeda G‐protein‐coupled receptor 5 for hepatic lipid metabolism in feast and famine

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Gut microbiota and cardiovascular disease.

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Role of bile acids in inflammatory liver diseases

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