Cited by 106Drug Transport and Resistance MechanismsLiver physiology and pathologyLiver Diseases and Immunity

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Role of TGR5 (GPBAR1) in Liver Disease

Häussinger, Dieter, Keitel, Verena·2018·Seminars in Liver Disease

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Abstract

TGR5 (GPBAR1) is a G protein–coupled receptor activated by primary and secondary bile acids, which is expressed in different nonparenchymal cells of the liver, such as sinusoidal endothelial cells, Kupffer cells, cholangiocytes as well as activated hepatic stellate cells. In liver, TGR5 modulates microcirculation, inflammation, regeneration, biliary secretion and proliferation as well as gallbladder filling. Absence of TGR5 renders mice more susceptible toward infectious, inflammatory, metabolic as well as cholestatic liver injuries. It is unknown whether TGR5 plays a role in the pathogenesis of human nonalcoholic steatohepatitis and cholestatic liver diseases such as primary sclerosing cholangitis and primary biliary cholangitis. However, overexpression of TGR5 has been detected in human intra- and extrahepatic cholangiocarcinoma as well as in cystic cholangiocytes, where the receptor promotes cell proliferation, anti-apoptosis as well as cyst growth. While TGR5 agonists may improve various aspects of metabolic, inflammatory, and cholestatic liver diseases, TGR5 inhibitors may attenuate disease progression in polycystic liver disease and cholangiocarcinoma.

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Additional file 3 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
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Additional file 2 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
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Additional file 8 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
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Additional file 5 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741366
Additional file 10 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741381
Additional file 7 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741372
Additional file 9 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741378
Additional file 11 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741384
Additional file 12 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741387
Additional file 1 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26143716
Additional file 4 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741363
Additional file 6 of Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis
Sun, L., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Figshare · doi:10.6084/m9.figshare.26741369
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
Cui, C., Sun, Y., Zhang, K., Shi, J., Wang, K., & Gao, S. (2026) · Drug Design Development and Therapy · doi:10.2147/dddt.s573597
Bile acids signaling as a novel mechanism in the hypothalamic control of energy balance.
Castellanos-Jankiewicz, A. (2019) · doi:10.70675/add823eez1845z4f7ezbe46zb57c0325a3fc

Authors: Häussinger, D., & Keitel, V.
Affiliations: Düsseldorf University Hospital (DE)
Corresponding author: Keitel, Verena
ORCID: Häussinger, Dieter
Keitel, Verena
Venue: Seminars in Liver Disease
Publisher: Georg Thieme Verlag KG
Published: 2018-10-24
Volume: 38
Issue: 04
Pages: 333-339
ISSN: 0272-8087 (ISSN-L)
1098-8971
DOI: 10.1055/s-0038-1669940
OpenAlex: W2898124054
Cited by: 106
References: 83
Citations by year: 2026: 8 · 2025: 13 · 2024: 20 · 2023: 15 · 2022: 11 · 2021: 21 · 2020: 12 · 2019: 6
FWCI: 3.66
Type: journal article
Language: en
Open access: closed
Locations: Seminars in Liver Disease (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords: TGR5, G protein-coupled receptors, bile acids, liver disease, cholestatic liver injury, nonalcoholic steatohepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, cholangiocarcinoma, polycystic liver disease, TGR5 agonists, hepatic stellate cells, Kupffer cells, cholangiocytes, liver regeneration, inflammation
MeSH terms: Animals, Bile Acids and Salts, Bile Duct Diseases, Cholestasis, Epithelial Cells, Humans, Hypertension, Portal, Liver Diseases, Signal Transduction, Cholangiocarcinoma, Receptors, G-Protein-Coupled, Mice

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Role of TGR5 (GPBAR1) in Liver Disease

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