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Original Article

Progress in research on the roles of TGR5 receptor in liver diseases

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Pages 717-726 | Received 30 Jan 2021, Accepted 08 Mar 2021, Published online: 26 Mar 2021

References

  • Merlen G, Bidault-Jourdainne V, Kahale N, et al. Hepatoprotective impact of the bile acid receptor TGR5. Liver Int. 2020;40(5):1005–1015.
  • Halilbasic E, Claudel T, Trauner M. Bile acid transporters and regulatory nuclear receptors in the liver and beyond. J Hepatol. 2013;58(1):155–168.
  • Chen X, Xu H, Ding L, et al. Identification of miR-26a as a target gene of bile acid receptor GPBAR-1/TGR5. PLoS One. 2015;10(6):e0131294.
  • Kawamata Y, Fujii R, Hosoya M, et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003;278(11):9435–9440.
  • Keitel V, Haussinger D. Perspective: TGR5 (Gpbar-1) in liver physiology and disease. Clin Res Hepatol Gastroenterol. 2012;36(5):412–419.
  • Sawitza I, Kordes C, Götze S, et al. Bile acids induce hepatic differentiation of mesenchymal stem cells. Sci Rep. 2015;5:13320.
  • Maruyama T, Tanaka K, Suzuki J, et al. Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. J Endocrinol. 2006;191(1):197–205.
  • Li T, Holmstrom SR, Kir S, et al. The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling. Mol Endocrinol. 2011;25(6):1066–1071.
  • Donepudi AC, Boehme S, Li F, et al. G-protein-coupled bile acid receptor plays a key role in bile acid metabolism and fasting-induced hepatic steatosis in mice. Hepatology. 2017;65(3):813–827.
  • Klindt C, Reich M, Hellwig B, et al. The G protein-coupled bile acid receptor TGR5 (Gpbar1) modulates endothelin-1 signaling in liver. Cells. 2019;8(11):1467.
  • Marrone G, Shah VH, Gracia-Sancho J. Sinusoidal communication in liver fibrosis and regeneration. J Hepatol. 2016;65(3):608–617.
  • Greuter T, Shah VH. Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights. J Gastroenterol. 2016;51(6):511–519.
  • McConnell M, Iwakiri Y. Biology of portal hypertension. Hepatol Int. 2018;12(Suppl 1):11–23.
  • Aydin MM, Akcali KC. Liver fibrosis. Turk J Gastroenterol. 2018;29(1):14–21.
  • Hammel P, Couvelard A, O'Toole D, et al. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med. 2001;344(6):418–423.
  • Krizhanovsky V, Yon M, Dickins RA, et al. Senescence of activated stellate cells limits liver fibrosis. Cell. 2008;134(4):657–667.
  • Passino MA, Adams RA, Sikorski SL, et al. Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR. Science. 2007;315(5820):1853–1856.
  • Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115(2):209–218.
  • Borkham-Kamphorst E, van Roeyen CR, Ostendorf T, et al. Pro-fibrogenic potential of PDGF-D in liver fibrosis. J Hepatol. 2007;46(6):1064–1074.
  • Yoshida S, Ikenaga N, Liu SB, et al. Extrahepatic platelet-derived growth factor-beta, delivered by platelets, promotes activation of hepatic stellate cells and biliary fibrosis in mice. Gastroenterology. 2014;147(6):1378–1392.
  • Ogawa S, Ochi T, Shimada H, et al. Anti-PDGF-B monoclonal antibody reduces liver fibrosis development. Hepatol Res. 2010;40(11):1128–1141.
  • Wang X, Gao Y, Li Y, et al. Roseotoxin B alleviates cholestatic liver fibrosis through inhibiting PDGF-B/PDGFR-β pathway in hepatic stellate cells. Cell Death Dis. 2020;11(6):458.
  • Borkham-Kamphorst E, Stoll D, Gressner AM, et al. Antisense strategy against PDGF B-chain proves effective in preventing experimental liver fibrogenesis. Biochem Biophys Res Commun. 2004;321(2):413–423.
  • Hao ZM, Fan XB, Li S, et al. Vaccination with platelet-derived growth factor B kinoids inhibits CCl-induced hepatic fibrosis in mice. J Pharmacol Exp Ther. 2012;342(3):835–842.
  • Wang X, Wu X, Zhang A, et al. Targeting the PDGF-B/PDGFR-β Interface with destruxin A5 to selectively block PDGF-BB/PDGFR-ββ signaling and attenuate liver fibrosis. EBioMedicine. 2016;7:146–156.
  • Schoemaker MH, Rots MG, Beljaars L, et al. PDGF-receptor beta-targeted adenovirus redirects gene transfer from hepatocytes to activated stellate cells. Mol Pharm. 2008;5(3):399–406.
  • Bai Q, An J, Wu X, et al. HBV promotes the proliferation of hepatic stellate cells via the PDGF-B/PDGFR-β signaling pathway in vitro. Int J Mol Med. 2012;30(6):1443–1450.
  • Ferrell JM, Pathak P, Boehme S, et al. Deficiency of both farnesoid X receptor and Takeda G protein-coupled receptor 5 exacerbated liver fibrosis in mice. Hepatology. 2019;70(3):955–970.
  • Kaji k, Yoshiji H, Kitade M, et al. Impact of insulin resistance on the progression of chronic liver diseases. Int J Mol Med. 2008;22:801–808.
  • Huang S, Ma S, Ning M, et al. TGR5 agonist ameliorates insulin resistance in the skeletal muscles and improves glucose homeostasis in diabetic mice. Metabolism. 2019;99:45–56.
  • Ding L, Sousa KM, Jin L, et al. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology. 2016;64(3):760–773.
  • Ullmer C, Alvarez Sanchez R, Sprecher U, et al. Systemic bile acid sensing by G protein-coupled bile acid receptor 1 (GPBAR1) promotes PYY and GLP-1 release. Br J Pharmacol. 2013;169(3):671–684.
  • Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8(12):728–742.
  • Vilsboll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771.
  • Kaya D, Kaji K, Tsuji Y, et al. TGR5 activation modulates an inhibitory effect on liver fibrosis development mediated by anagliptin in diabetic rats. Cells. 2019;8(10):1153.
  • Lu YF, Wan XL, Xu Y, et al. Repeated oral administration of oleanolic acid produces cholestatic liver injury in mice. Molecules. 2013;18(3):3060–3071.
  • Weiskirchen R. Hepatoprotective and anti-fibrotic agents: it's time to take the next step. Front Pharmacol. 2015;6:303.
  • Tacke F, Weiskirchen R. An update on the recent advances in antifibrotic therapy. Expert Rev Gastroenterol Hepatol. 2018;12(11):1143–1152.
  • Wang YD, Chen WD, Yu D, et al. The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor κ light-chain enhancer of activated B cells (NF-κB) in mice. Hepatology. 2011;54(4):1421–1432.
  • Xiao H, Sun X, Liu R, et al. Gentiopicroside activates the bile acid receptor Gpbar1 (TGR5) to repress NF-kappaB pathway and ameliorate diabetic nephropathy. Pharmacol Res. 2020;151:104559.
  • Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14(7):397–411.
  • Rockey DC, Du Q, Weymouth ND, et al. Smooth muscle α-actin deficiency leads to decreased liver fibrosis via impaired cytoskeletal signaling in hepatic stellate cells. Am J Pathol. 2019;189(11):2209–2220.
  • Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10(3):170–181.
  • Geissmann F, Cameron TO, Sidobre S, et al. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol. 2005;3(4):e113.
  • Ishikawa S, Ikejima K, Yamagata H, et al. CD1d-restricted natural killer T cells contribute to hepatic inflammation and fibrogenesis in mice. J Hepatol. 2011;54(6):1195–1204.
  • Perino A, Pols TW, Nomura M, et al. TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation. J Clin Invest. 2014;124(12):5424–5436.
  • Wu SJ, Yang YH, Tsuneyama K, et al. Innate immunity and primary biliary cirrhosis: activated invariant natural killer T cells exacerbate murine autoimmune cholangitis and fibrosis. Hepatology. 2011;53(3):915–925.
  • Takeda K, Hayakawa Y, Van Kaer L, et al. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc Natl Acad Sci USA. 2000;97(10):5498–5503.
  • Biburger M, Tiegs G. Alpha-galactosylceramide-induced liver injury in mice is mediated by TNF-alpha but independent of Kupffer cells. J Immunol. 2005;175(3):1540–1550.
  • Biagioli M, Carino A, Fiorucci C, et al. GPBAR1 functions as gatekeeper for liver NKT cells and provides counterregulatory signals in mouse models of immune-mediated hepatitis. Cell Mol Gastroenterol Hepatol. 2019;8(3):447–473.
  • Ito K, Okumura A, Junko ST, et al. Dual agonist of farnesoid X receptor and G protein-coupled receptor TGR5 inhibits hepatitis B virus infection in vitro and in vivo. Hepatology. 2021. DOI:10.1002/hep.31712
  • Gao S, Ji XF, Li F, et al. Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 predicts prognosis of acute-on-chronic hepatitis B liver failure. J Viral Hepat. 2015;22(2):112–119.
  • Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84.
  • Pompili S, Vetuschi A, Gaudio E, et al. Long-term abuse of a high-carbohydrate diet is as harmful as a high-fat diet for development and progression of liver injury in a mouse model of NAFLD/NASH. Nutrition. 2020;75-76:110782.
  • Ding X, Saxena NK, Lin S, et al. Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology. 2006;43(1):173–181.
  • Mells JE, Fu PP, Sharma S, et al. Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. Am J Physiol Gastrointest Liver Physiol. 2012;302(2):G225–G235.
  • Trevaskis JL, Griffin PS, Wittmer C, et al. Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol. 2012;302(8):G762–G772.
  • Yang H, Yang T, Heng C, et al. Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice. Phytother Res. 2019;33(12):3140–3152.
  • Carino A, Cipriani S, Marchiano S, et al. Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice. Sci Rep. 2017;7(1):13689.
  • Bertholet AM, Kazak L, Chouchani ET, et al. Mitochondrial patch clamp of beige adipocytes reveals UCP1-positive and UCP1-negative cells both exhibiting futile creatine cycling. Cell Metab. 2017;25(4):811–822 e4.
  • Herzig S, Long F, Jhala US, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature. 2001;413(6852):179–183.
  • Oni ET, Agatston AS, Blaha MJ, et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis. 2013;230(2):258–267.
  • Kim D, Choi SY, Park EH, et al. Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology. 2012;56(2):605–613.
  • Sinn DH, Cho SJ, Gu S, et al. Persistent nonalcoholic fatty liver disease increases risk for carotid atherosclerosis. Gastroenterology. 2016;151(3):481–488 e1.
  • European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–1402.
  • Targher G, Marra F, Marchesini G. Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? Diabetologia. 2008;51(11):1947–1953.
  • Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol. 2016;65(2):425–443.
  • Arulanandan A, Ang B, Bettencourt R, et al. Association between quantity of liver fat and cardiovascular risk in patients with nonalcoholic fatty liver disease independent of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2015;13(8):1513–1520e1.
  • Zeb I, Li D, Budoff MJ, et al. Nonalcoholic fatty liver disease and incident cardiac events: the multi-ethnic study of atherosclerosis. J Am Coll Cardiol. 2016;67(16):1965–1966.
  • Carino A, Marchiano S, Biagioli M, et al. Agonism for the bile acid receptor GPBAR1 reverses liver and vascular damage in a mouse model of steatohepatitis. Faseb J. 2019;33(2):2809–2822.
  • Gong Z, Zhou J, Zhao S, et al. Chenodeoxycholic acid activates NLRP3 inflammasome and contributes to cholestatic liver fibrosis. Oncotarget. 2016;7(51):83951–83963.
  • Merlen G, Ursic-Bedoya J, Jourdainne V, et al. Bile acids and their receptors during liver regeneration: “Dangerous protectors”. Mol Aspects Med. 2017;56:25–33.
  • Huang W, Ma K, Zhang J, et al. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science. 2006;312(5771):233–236.
  • Bhushan B, Borude P, Edwards G, et al. Role of bile acids in liver injury and regeneration following acetaminophen overdose. Am J Pathol. 2013;183(5):1518–1526.
  • Starkel P, Shindano T, Horsmans Y, et al. Foetal 'flat' bile acids reappear during human liver regeneration after surgery. Eur J Clin Invest. 2009;39(1):58–64.
  • Miura T, Kimura N, Yamada T, et al. Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90% partial hepatectomy. J Hepatol. 2011;55(2):407–414.
  • Fahrner R, Patsenker E, de Gottardi A, et al. Elevated liver regeneration in response to pharmacological reduction of elevated portal venous pressure by terlipressin after partial hepatectomy. Transplantation. 2014;97(9):892–900.
  • Pean N, Doignon I, Garcin I, et al. The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice. Hepatology. 2013;58(4):1451–1460.
  • Spirli C, Nathanson MH, Fiorotto R, et al. Proinflammatory cytokines inhibit secretion in rat bile duct epithelium. Gastroenterology. 2001;121(1):156–169.
  • Merlen G, Kahale N, Ursic-Bedoya J, et al. TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function. Gut. 2020;69(1):146–157.
  • Keitel V, Cupisti K, Ullmer C, et al. The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders. Hepatology. 2009;50(3):861–870.
  • Beuers U, Hohenester S, de Buy Wenniger LJ, et al. The biliary HCO(3)(-) umbrella: a unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies. Hepatology. 2010;52(4):1489–1496.
  • Hov JR, Keitel V, Laerdahl JK, IBSEN Study Group, et al. Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis. PLoS One. 2010;5(8):e12403.
  • Pradhan-Sundd T, Zhou L, Vats R, et al. Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis. Hepatology. 2018;67(6):2320–2337.
  • Matsumoto K, Imasato M, Yamazaki Y, et al. Claudin 2 deficiency reduces bile flow and increases susceptibility to cholesterol gallstone disease in mice. Gastroenterology. 2014;147(5):1134–1145 e10.
  • Boyer JL. The hepatobiliary paracellular pathway: a paradigm revisited. Gastroenterology. 2014;147(5):965–968.
  • Sakisaka S, Kawaguchi T, Taniguchi E, et al. Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology. 2001;33(6):1460–1468.
  • Fickert P, Fuchsbichler A, Wagner M, et al. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology. 2004;127(1):261–274.
  • Hadj-Rabia S, Baala L, Vabres P, et al. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 2004;127(5):1386–1390.
  • Ebnet K. Junctional adhesion molecules (JAMs): cell adhesion receptors with pleiotropic functions in cell physiology and development. Physiol Rev. 2017;97(4):1529–1554.
  • Grosse B, Degrouard J, Jaillard D, et al. Build them up and break them down: tight junctions of cell lines expressing typical hepatocyte polarity with a varied repertoire of claudins. Tissue Barriers. 2013;1(4):e25210.
  • Monga SP. Role of Wnt/β-catenin signaling in liver metabolism and cancer. Int J Biochem Cell Biol. 2011;43(7):1021–1029.
  • Sun J, Hobert ME, Duan Y, et al. Crosstalk between NF-kappaB and beta-catenin pathways in bacterial-colonized intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2005;289(1):G129–G137.
  • Ke B, Shen XD, Kamo N, et al. β-catenin regulates innate and adaptive immunity in mouse liver ischemia–reperfusion injury. Hepatology. 2013;57(3):1203–1214.
  • Rao J, Yang C, Yang S, et al. Deficiency of TGR5 exacerbates immune-mediated cholestatic hepatic injury by stabilizing the β-catenin destruction complex. Int Immunol. 2020;32(5):321–334.
  • Yue S, Zhu J, Zhang M, et al. The myeloid heat shock transcription factor 1/β-catenin axis regulates NLR family, pyrin domain-containing 3 inflammasome activation in mouse liver ischemia/reperfusion injury. Hepatology. 2016;64(5):1683–1698.
  • Rao J, Qin J, Qian X, et al. Lipopolysaccharide preconditioning protects hepatocytes from ischemia/reperfusion injury (IRI) through inhibiting ATF4–CHOP pathway in mice. PLoS One. 2013;8(6):e65568.
  • Jaeschke H, Woolbright BL. Current strategies to minimize hepatic ischemia–reperfusion injury by targeting reactive oxygen species. Transplant Rev (Orlando). 2012;26(2):103–114.
  • Que X, Debonera F, Xie J, et al. Pattern of ischemia reperfusion injury in a mouse orthotopic liver transplant model. J Surg Res. 2004;116(2):262–268.
  • Rao J, Yue S, Fu Y, et al. ATF6 mediates a pro-inflammatory synergy between ER stress and TLR activation in the pathogenesis of liver ischemia–reperfusion injury. Am J Transplant. 2014;14(7):1552–1561.
  • Rao J, Qian X, Li G, et al. ATF3-mediated NRF2/HO-1 signaling regulates TLR4 innate immune responses in mouse liver ischemia/reperfusion injury. Am J Transplant. 2015;15(1):76–87.
  • Kaczorowski DJ, Tsung A, Billiar TR. Innate immune mechanisms in ischemia/reperfusion. Front Biosci (Elite Ed). 2009;1:91–98.
  • Vilatoba M, Eckstein C, Bilbao G, et al. Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis. Surgery. 2005;138(2):342–351.
  • Liu J, Ren F, Cheng Q, et al. Endoplasmic reticulum stress modulates liver inflammatory immune response in the pathogenesis of liver ischemia and reperfusion injury. Transplantation. 2012;94(3):211–217.
  • Zhuang L, Fan Y, Lu L, et al. Ischemic preconditioning protects hepatocytes from ischemia–reperfusion injury via TGR5-mediated anti-apoptosis. Biochem Biophys Res Commun. 2016;473(4):966–972.
  • Yang H, Zhou H, Zhuang L, et al. Plasma membrane-bound G protein-coupled bile acid receptor attenuates liver ischemia/reperfusion injury via the inhibition of toll-like receptor 4 signaling in mice. Liver Transpl. 2017;23(1):63–74.
  • Keitel V, Reinehr R, Gatsios P, et al. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells. Hepatology. 2007;45(3):695–704.
  • Renga B, Bucci M, Cipriani S, et al. Cystathionine γ-lyase, a H2S-generating enzyme, is a GPBAR1-regulated gene and contributes to vasodilation caused by secondary bile acids. Am J Physiol Heart Circ Physiol. 2015;309(1):H114–H126.
  • Renga B, Cipriani S, Carino A, et al. Reversal of endothelial dysfunction by GPBAR1 agonism in portal hypertension involves a AKT/FOXOA1 dependent regulation of H2S generation and endothelin-1. PLoS One. 2015;10(11):e0141082.
  • Keitel V, Stindt J, Haussinger D. Bile acid-activated receptors: GPBAR1 (TGR5) and other G protein-coupled receptors. Handb Exp Pharmacol. 2019;256:19–49.
  • Keitel V, Haussinger D. Role of TGR5 (GPBAR1) in liver disease. Semin Liver Dis. 2018;38(4):333–339.
  • Ho FM, Lin WW, Chen BC, et al. High glucose-induced apoptosis in human vascular endothelial cells is mediated through NF-kappaB and c-Jun NH2-terminal kinase pathway and prevented by PI3K/Akt/eNOS pathway. Cell Signal. 2006;18(3):391–399.
  • Kida T, Tsubosaka Y, Hori M, et al. Bile acid receptor TGR5 agonism induces NO production and reduces monocyte adhesion in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33(7):1663–1669.
  • Guizoni DM, Vettorazzi JF, Carneiro EM, et al. Modulation of endothelium-derived nitric oxide production and activity by taurine and taurine-conjugated bile acids. Nitric Oxide. 2020;94:48–53.
  • Michell BJ, Chen Z, Tiganis T, et al. Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem. 2001;276:17625–17628.
  • Reich M, Deutschmann K, Sommerfeld A, et al. TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro. Gut. 2016;65(3):487–501.
  • Masyuk TV, Masyuk AI, Lorenzo Pisarello M, et al. TGR5 contributes to hepatic cystogenesis in rodents with polycystic liver diseases through cyclic adenosine monophosphate/Gαs signaling. Hepatology. 2017;66(4):1197–1218.
  • Masyuk TV, Masyuk AI, LaRusso NF. TGR5 in the cholangiociliopathies. Dig Dis. 2015;33(3):420–425.
  • Cao W, Tian W, Hong J, et al. Expression of bile acid receptor TGR5 in gastric adenocarcinoma. Am J Physiol Gastrointest Liver Physiol. 2013;304(4):G322–G327.
  • Casaburi I, Avena P, Lanzino M, et al. Chenodeoxycholic acid through a TGR5-dependent CREB signaling activation enhances cyclin D1 expression and promotes human endometrial cancer cell proliferation. Cell Cycle. 2012;11(14):2699–2710.
  • Li AD, Xie XL, Qi W, et al. TGR5 promotes cholangiocarcinoma by interacting with mortalin. Exp Cell Res. 2020;389(2):111855.
  • Khan SA, Davidson BR, Goldin RD, et al.; British Society of Gastroenterology. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61(12):1657–1669.
  • Mittal PK, Moreno CC, Kalb B, et al. Primary biliary tract malignancies: MRI spectrum and mimics with histopathological correlation. Abdom Imaging. 2015;40(6):1520–1557.
  • Erice O, Labiano I, Arbelaiz A, et al. Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4 Pt B):1335–1344.
  • Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009;361(15):1437–1447.
  • Zhou J, Yu L, Gao X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol. 2011;29(36):4781–4788.
  • Jones KR, Nabinger SC, Lee S, et al. Lower expression of tumor microRNA-26a is associated with higher recurrence in patients with hepatocellular carcinoma undergoing surgical treatment. J Surg Oncol. 2018;118:431–439.
  • Ma Y, Deng F, Li P, et al. The tumor suppressive miR-26a regulation of FBXO11 inhibits proliferation, migration and invasion of hepatocellular carcinoma cells. Biomed Pharmacother. 2018;101:648–655.
  • Gupta P, Sata TN, Ahamad N, et al. Augmenter of liver regeneration enhances cell proliferation through the microRNA-26a/Akt/cyclin D1 pathway in hepatic cells. Hepatol Res. 2019;49(11):1341–1352.
  • Ali O, Darwish HA, Eldeib KM, et al. miR-26a potentially contributes to the regulation of fatty acid and sterol metabolism in vitro human hepG2 cell model of nonalcoholic fatty liver disease. Oxid Med Cell Longev. 2018;2018:8515343.