# The role of bile acid-activated receptor TGR5 in inflammation and liver diseases

**Authors:** Hongyan Xiang, Huanyu Xiang, Shuyun Wang, Peiyu Wu, Zhidan Luo, Jie Zhang

PMC · DOI: 10.3389/fphys.2026.1747341 · Frontiers in Physiology · 2026-02-17

## TL;DR

This review explores how the bile acid receptor TGR5 influences liver diseases and inflammation, highlighting its potential as a therapeutic target.

## Contribution

The paper provides a comprehensive review of TGR5's role in liver diseases and its potential as a therapeutic target.

## Key findings

- TGR5 activation can reduce inflammation and metabolic disorders in liver diseases.
- TGR5 is involved in various liver pathologies like steatohepatitis and hepatocellular carcinoma.
- TGR5 has regulatory functions in immune cells and inflammatory pathways.

## Abstract

Takeda G-protein-coupled receptor 5 (TGR5), a bile acid receptor, has been recognized as an important signal molecule with roles extending far beyond bile acid homeostasis. Its activation has been shown to ameliorate metabolic disorders and suppress inflammatory responses through diverse mechanisms. Expressed widely in both parenchymal and non-parenchymal cells of the liver, TGR5 plays a central role in hepatic physiology and disease. This review consolidates current evidence on the involvement of TGR5 in various liver pathologies, including metabolic dysfunction-associated steatohepatitis, cholestatic diseases, liver fibrosis, and hepatocellular carcinoma. Additionally, we summarize the regulatory functions of TGR5 in immune cells and inflammatory signaling pathways. We emphasize TGR5 as a promising therapeutic target for a range of chronic liver diseases, given its pivotal role in modulating inflammation and metabolism. Future research should focus on developing tissue-specific TGR5 agonists to enhance therapeutic efficacy and reduce systemic side effects, as well as elucidating its context-dependent dual roles in hepatocarcinogenesis to ensure safe clinical application.

## Linked entities

- **Genes:** GPBAR1 (G protein-coupled bile acid receptor 1) [NCBI Gene 151306]
- **Diseases:** metabolic dysfunction-associated steatohepatitis (MONDO:0007027), hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** FGF19 (fibroblast growth factor 19) [NCBI Gene 9965], Acly (ATP citrate lyase) [NCBI Gene 24159] {aka ACL, Clatp}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, Egfr (epidermal growth factor receptor) [NCBI Gene 24329] {aka ERBB1, ErbB-1, Errp}, F11r (F11 receptor) [NCBI Gene 116479] {aka Jam1}, Nfkbia (NFKB inhibitor alpha) [NCBI Gene 25493] {aka RL/IF-1}, Gpbar1 (G protein-coupled bile acid receptor 1) [NCBI Gene 338443] {aka M-BAR, Tgr5}, Gcg (glucagon) [NCBI Gene 14526] {aka GLP-1, Glu, PPG}, Syt1 (synaptotagmin 1) [NCBI Gene 25716] {aka P65}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, Nr1h4 (nuclear receptor subfamily 1, group H, member 4) [NCBI Gene 20186] {aka Fxr, HRR1, RIP14, Rxrip14}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, ROCK1 (Rho associated coiled-coil containing protein kinase 1) [NCBI Gene 6093] {aka P160ROCK, ROCK-I}, Gast (gastrin) [NCBI Gene 25320] {aka Gas, PPG34}, Lipe (lipase E, hormone sensitive type) [NCBI Gene 16890] {aka 4933403G17Rik, HSL, REH}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Cth (cystathionine gamma-lyase) [NCBI Gene 24962] {aka CGL, CSE}, Nr1h4 (nuclear receptor subfamily 1, group H, member 4) [NCBI Gene 60351] {aka Fxr}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, Krt19 (keratin 19) [NCBI Gene 360626] {aka Ka19, Krt1-19}, Gcg (glucagon) [NCBI Gene 24952] {aka GLP-1, Glp1, Glp2}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, Edn1 (endothelin 1) [NCBI Gene 24323] {aka Et1}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, Crebbp (CREB binding lysine acetyltransferase) [NCBI Gene 54244] {aka CBP, RSTS, RTS}, Nos3 (nitric oxide synthase 3) [NCBI Gene 24600] {aka eNos}, CHRNA7 (cholinergic receptor nicotinic alpha 7 subunit) [NCBI Gene 1139] {aka CHRNA7-2, NACHRA7, a7nAChR, nAChR7}, Arrb2-ps (arrestin, beta 2, pseudogene) [NCBI Gene 365541] {aka Arrb2}, Prkaca (protein kinase cAMP-activated catalytic subunit alpha) [NCBI Gene 25636] {aka Cs-PKA, PKCA1}, Pycard (PYD and CARD domain containing) [NCBI Gene 282817] {aka Asc}, Rxfp2 (relaxin family peptide receptor 2) [NCBI Gene 363866] {aka Gpcr, Lgr8}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 81646] {aka Creb}, Sp1 (Sp1 transcription factor) [NCBI Gene 24790], Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Foxo1 (forkhead box O1) [NCBI Gene 84482] {aka Fkhr, Foxo1a}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, Pyy (peptide YY) [NCBI Gene 287730] {aka GHYY, RATGHYY, Yy, peptide-YY}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}
- **Diseases:** cholecystitis (MESH:D002764), hepatic oncogenesis (MESH:D063646), obese (MESH:D009765), MASH (MESH:D005234), pruritus (MESH:D011537), metabolic diseases (MESH:D008659), cirrhotic (MESH:D000094724), cirrhosis (MESH:D005355), Cholestatic liver diseases (MESH:D008107), hepatic inflammation (MESH:D007249), Liver fibrosis (MESH:D008103), diabetes (MESH:D003920), cancer (MESH:D009369), psychiatric illnesses (MESH:D001523), NAFLD (MESH:D065626), cholestatic liver disorders (MESH:D017093), hepatic pathologies (MESH:D005598), type 2 diabetes (MESH:D003924), cholestasis-related diseases (MESH:C535932), PSC (MESH:D015209), hepatic lipid (MESH:D011017), cholelithiasis (MESH:D002769), HCC (MESH:D006528), HCC precancerous lesions (MESH:D011230), bone metastasis (MESH:D009362), hepatic insulin resistance (MESH:D007333), hepatobiliary injury (MESH:D004066), toxicity (MESH:D064420), cholestasis (MESH:D002779), cardiovascular disorders (MESH:D002318)
- **Chemicals:** free fatty acids (MESH:D005230), glycogen (MESH:D006003), cAMP (MESH:D000242), INT-767 (MESH:C000602622), chloride (MESH:D002712), cholesterol (MESH:D002784), BAR502 (MESH:C000656652), DCA (MESH:D003840), CA (MESH:D019826), triglycerides (MESH:D014280), LPS (MESH:D008070), lipid (MESH:D008055), BAs (MESH:D001464), BAR501 (MESH:C000608430), glucose (MESH:D005947), curcumin (MESH:D003474), BA (MESH:D001647), GlaxoSmithKline (-), bicarbonate (MESH:D001639), LCA (MESH:D008095), CDCA (MESH:D002635)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

108 references — full list in the complete paper: https://tomesphere.com/paper/PMC12953091/full.md

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Source: https://tomesphere.com/paper/PMC12953091