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Cholangiopathies are also associated with cholestasis, which is the retention of biliary components, including bile acids, in the liver and blood. Cholestasis may worsen with biliary fibrosis. Furthermore, bile acid levels, composition and homeostasis are dysregulated in PBC and PSC. In fact, mounting data from animal models and human cholangiopathies suggest that bile acids play a crucial role in the pathogenesis and progression of biliary fibrosis. The identification of bile acid receptors has advanced our understanding of various signaling pathways involved in regulating cholangiocyte functions and the potential impact on biliary fibrosis. We will also briefly review recent findings linking these receptors with epigenetic regulatory mechanisms. Further detailed understanding of bile acid signaling in the pathogenesis of biliary fibrosis will uncover additional therapeutic avenues for cholangiopathies.<\/jats:p>","DOI":"10.3390\/cells12050792","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T02:56:50Z","timestamp":1677812210000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Bile Acids and Biliary Fibrosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3234-1769","authenticated-orcid":false,"given":"Sayed Obaidullah","family":"Aseem","sequence":"first","affiliation":[{"name":"Stravitz-Sanyal Institute for Liver Disease & Metabolic Health, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip B.","family":"Hylemon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Central Virginia Veterans Healthcare System, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-372X","authenticated-orcid":false,"given":"Huiping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Central Virginia Veterans Healthcare System, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1053\/j.gastro.2004.08.006","article-title":"The cholangiopathies: Disorders of biliary epithelia","volume":"127","author":"Lazaridis","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.jhep.2017.07.022","article-title":"Primary sclerosing cholangitis\u2014A comprehensive review","volume":"67","author":"Karlsen","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Park, J.-W., Kim, J.-H., Kim, S.-E., Jung, J.H., Jang, M.-K., Park, S.-H., Lee, M.-S., Kim, H.-S., Suk, K.T., and Kim, D.J. (2022). Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: Current Knowledge of Pathogenesis and Therapeutics. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061288"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.4254\/wjh.v12.i8.423","article-title":"Review: Pathogenesis of cholestatic liver diseases","volume":"12","author":"Yokoda","year":"2020","journal-title":"World J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41575-022-00687-7","article-title":"Mechanisms of pruritus in cholestasis: Understanding and treating the itch","volume":"20","author":"Beuers","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/MOG.0000000000000805","article-title":"Cellular senescence in the cholangiopathies","volume":"38","author":"Bogert","year":"2022","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41575-021-00566-7","article-title":"Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology","volume":"19","author":"Fuchs","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.steroids.2014.04.016","article-title":"Bile acids are nutrient signaling hormones","volume":"86","author":"Zhou","year":"2014","journal-title":"Steroids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jhep.2021.02.011","article-title":"Bile formation and secretion: An update","volume":"75","author":"Boyer","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.3748\/wjg.v12.i22.3553","article-title":"Bile acid interactions with cholangiocytes","volume":"12","author":"Xia","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1194\/jlr.R500013-JLR200","article-title":"Bile salt biotransformations by human intestinal bacteria","volume":"47","author":"Ridlon","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0022-2275(20)37923-2","article-title":"General methods for the analysis of metabolic profiles of bile acids and related compounds in feces","volume":"24","author":"Setchell","year":"1983","journal-title":"J. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41575-019-0125-y","article-title":"Cholangiocyte pathobiology","volume":"16","author":"Banales","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.bbadis.2017.06.017","article-title":"Mechanisms of cholangiocyte responses to injury","volume":"1864","author":"Sato","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.jhep.2017.04.026","article-title":"Biliary bile acids in hepatobiliary injury\u2014What is the link?","volume":"67","author":"Fickert","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cld.2018.03.013","article-title":"Role of Bile Acids and the Biliary HCO(3)(\u2212) Umbrella in the Pathogenesis of Primary Biliary Cholangitis","volume":"22","author":"Kersten","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12016-019-08731-2","article-title":"Comprehensive Analysis of Serum and Fecal Bile Acid Profiles and Interaction with Gut Microbiota in Primary Biliary Cholangitis","volume":"58","author":"Chen","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/hep.31652","article-title":"Bile Acid Profiles in Primary Sclerosing Cholangitis and Their Ability to Predict Hepatic Decompensation","volume":"74","author":"Mousa","year":"2021","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"433","DOI":"10.4254\/wjh.v13.i4.433","article-title":"Bile acid indices as biomarkers for liver diseases I: Diagnostic markers","volume":"13","author":"Alamoudi","year":"2021","journal-title":"World J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1177\/2050640617708953","article-title":"The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease","volume":"6","author":"Torres","year":"2018","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.dld.2011.10.025","article-title":"Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: A pilot study","volume":"44","author":"Trottier","year":"2012","journal-title":"Dig. Liver Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1136\/gutjnl-2019-318416","article-title":"Alterations of the bile microbiome in primary sclerosing cholangitis","volume":"69","author":"Liwinski","year":"2020","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5454","DOI":"10.3748\/wjg.v19.i33.5454","article-title":"Biliary phosphatidylcholine and lysophosphatidylcholine profiles in sclerosing cholangitis","volume":"19","author":"Gauss","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1111\/liv.13092","article-title":"Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis","volume":"36","author":"Zweers","year":"2016","journal-title":"Liver Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0016-5085(71)80053-7","article-title":"Bile acid metabolism in patients with cirrhosis. I. Kinetic aspects of cholic acid metabolism","volume":"60","author":"Vlahcevic","year":"1971","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1136\/gut.14.11.895","article-title":"Cholic acid synthesis as an index of the severity of liver disease in man","volume":"14","author":"McCormick","year":"1973","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.taap.2015.01.015","article-title":"Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis","volume":"283","author":"Woolbright","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"410","DOI":"10.2353\/ajpath.2006.050404","article-title":"Lithocholic acid feeding induces segmental bile duct obstruction and destructive cholangitis in mice","volume":"168","author":"Fickert","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1124\/jpet.119.256255","article-title":"Inhibition of Human Sulfotransferase 2A1-Catalyzed Sulfonation of Lithocholic Acid, Glycolithocholic Acid, and Taurolithocholic Acid by Selective Estrogen Receptor Modulators and Various Analogs and Metabolites","volume":"369","author":"Bansal","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/S0022-2275(20)35729-1","article-title":"Comparative binding of bile acids to serum lipoproteins and albumin","volume":"34","author":"Ceryak","year":"1993","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1002\/hep4.1998","article-title":"Tetrahydroxylated bile acids improve cholestatic liver and bile duct injury in the Mdr2(-\/-) mouse model of sclerosing cholangitis via immunomodulatory effects","volume":"6","author":"Fuchs","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.29076","article-title":"The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice","volume":"65","author":"Wang","year":"2017","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e90780","DOI":"10.1172\/jci.insight.90780","article-title":"Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response","volume":"2","author":"Cai","year":"2017","journal-title":"JCI Insight"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jhep.2012.02.014","article-title":"Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health","volume":"57","author":"Dilger","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0092-8674(93)90380-9","article-title":"Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease","volume":"75","author":"Smit","year":"1993","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jhep.2005.06.025","article-title":"Mdr2 (Abcb4)-\/- mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes","volume":"43","author":"Popov","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1053\/gast.2001.23984","article-title":"The wide spectrum of multidrug resistance 3 deficiency: From neonatal cholestasis to cirrhosis of adulthood","volume":"120","author":"Jacquemin","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/hep.24691","article-title":"A biliary HCO3- umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes","volume":"55","author":"Hohenester","year":"2012","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/hep.510250104","article-title":"Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis","volume":"25","author":"Medina","year":"1997","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0168-8278(03)00096-5","article-title":"Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis","volume":"38","author":"Zollner","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zimny, S., Koob, D., Li, J., Wimmer, R., Schiergens, T., Nagel, J., Reiter, F.P., Denk, G., and Hohenester, S. (2022). Hydrophobic Bile Salts Induce Pro-Fibrogenic Proliferation of Hepatic Stellate Cells through PI3K p110 Alpha Signaling. Cells, 11.","DOI":"10.3390\/cells11152344"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103290","DOI":"10.1016\/j.ebiom.2021.103290","article-title":"Conjugated secondary 12alpha-hydroxylated bile acids promote liver fibrogenesis","volume":"66","author":"Xie","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/hep.27240","article-title":"Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: Conjugated hypercholanemia without a clear clinical phenotype","volume":"61","author":"Vaz","year":"2015","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Xue, R., Su, L., Lai, S., Wang, Y., Zhao, D., Fan, J., Chen, W., Hylemon, P.B., and Zhou, H. (2021). Bile Acid Receptors and the Gut-Liver Axis in Nonalcoholic Fatty Liver Disease. Cells, 10.","DOI":"10.3390\/cells10112806"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"G1013","DOI":"10.1152\/ajpgi.00383.2012","article-title":"Ciliary subcellular localization of TGR5 determines the cholangiocyte functional response to bile acid signaling","volume":"304","author":"Masyuk","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.bbadis.2017.06.006","article-title":"The cholangiocyte primary cilium in health and disease","volume":"1864","author":"Mansini","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/modpathol.2011.212","article-title":"Cholangiocyte cilia are abnormal in syndromic and non-syndromic biliary atresia","volume":"25","author":"Chu","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1002\/dvdy.21530","article-title":"Cholangiocyte primary cilia in liver health and disease","volume":"237","author":"Masyuk","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/gutjnl-2015-309458","article-title":"TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro","volume":"65","author":"Reich","year":"2016","journal-title":"Gut"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.bbadis.2017.08.021","article-title":"Bile acid receptors in the biliary tree: TGR5 in physiology and disease","volume":"1864","author":"Deutschmann","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1210\/me.2010-0460","article-title":"The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling","volume":"25","author":"Li","year":"2011","journal-title":"Mol. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/MOG.0b013e32835f3f14","article-title":"TGR5 in cholangiocytes","volume":"29","author":"Keitel","year":"2013","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1053\/j.gastro.2003.09.044","article-title":"Inhibition of bile salt-induced apoptosis by cyclic AMP involves serine\/threonine phosphorylation of CD95","volume":"126","author":"Reinehr","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/hep.24537","article-title":"Dual farnesoid X receptor\/TGR5 agonist INT-767 reduces liver injury in the Mdr2-\/- (Abcb4-\/-) mouse cholangiopathy model by promoting biliary HCO(-)(3) output","volume":"54","author":"Baghdasaryan","year":"2011","journal-title":"Hepatology"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kaya, D., Kaji, K., Tsuji, Y., Yamashita, S., Kitagawa, K., Ozutsumi, T., Fujinaga, Y., Takaya, H., Kawaratani, H., and Moriya, K. (2019). TGR5 Activation Modulates an Inhibitory Effect on Liver Fibrosis Development Mediated by Anagliptin in Diabetic Rats. Cells, 8.","DOI":"10.3390\/cells8101153"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lou, G., Ma, X., Fu, X., Meng, Z., Zhang, W., Wang, Y.D., Van Ness, C., Yu, D., Xu, R., and Huang, W. (2014). GPBAR1\/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093567"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"21805","DOI":"10.1074\/jbc.C000275200","article-title":"Bile acid induction of cytokine expression by macrophages correlates with repression of hepatic cholesterol 7alpha-hydroxylase","volume":"275","author":"Miyake","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.cmet.2011.11.006","article-title":"TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading","volume":"14","author":"Pols","year":"2011","journal-title":"Cell Metab."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ignat, S.-R., Dinescu, S., Hermenean, A., and Costache, M. (2020). Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development. Cells, 9.","DOI":"10.3390\/cells9020461"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver inflammation and fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3389\/fmed.2020.00544","article-title":"Bile Acids and FXR: Novel Targets for Liver Diseases","volume":"7","author":"Stofan","year":"2020","journal-title":"Front. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1101\/gad.1773909","article-title":"Bile acid signaling pathways increase stability of Small Heterodimer Partner (SHP) by inhibiting ubiquitin-proteasomal degradation","volume":"23","author":"Miao","year":"2009","journal-title":"Genes Dev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/hep.22519","article-title":"Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response","volume":"48","author":"Wang","year":"2008","journal-title":"Hepatology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1136\/gut.2010.212159","article-title":"Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease","volume":"60","author":"Gadaleta","year":"2011","journal-title":"Gut"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.bbadis.2011.04.005","article-title":"Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-kappaB signaling in the intestine","volume":"1812","author":"Gadaleta","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1021\/mp060010s","article-title":"Role of nuclear receptors in the adaptive response to bile acids and cholestasis: Pathogenetic and therapeutic considerations","volume":"3","author":"Zollner","year":"2006","journal-title":"Mol. Pharm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11323","DOI":"10.1073\/pnas.0604772103","article-title":"Benefit of farnesoid X receptor inhibition in obstructive cholestasis","volume":"103","author":"Stedman","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1172\/JCI18945","article-title":"Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis","volume":"112","author":"Liu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13462","DOI":"10.1038\/srep13462","article-title":"Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease","volume":"5","author":"Wunsch","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"39573","DOI":"10.1038\/srep39573","article-title":"Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis","volume":"6","author":"Milkiewicz","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1124\/jpet.105.085597","article-title":"Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis","volume":"315","author":"Fiorucci","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.2353\/ajpath.2009.090114","article-title":"Farnesoid X receptor critically determines the fibrotic response in mice but is expressed to a low extent in human hepatic stellate cells and periductal myofibroblasts","volume":"175","author":"Fickert","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1096\/fba.2018-00046","article-title":"Bile acid receptor agonists in primary biliary cholangitis: Regulation of the cholangiocyte secretome and downstream T cell differentiation","volume":"1","author":"Etherington","year":"2019","journal-title":"FASEB Bioadv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1111\/ajt.12479","article-title":"Repression of Farnesoid X receptor contributes to biliary injuries of liver grafts through disturbing cholangiocyte bile acid transport","volume":"13","author":"Cheng","year":"2013","journal-title":"Am. J. Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1038\/ncomms10713","article-title":"Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis","volume":"7","author":"Potter","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.cgh.2019.09.050","article-title":"Long-Term Obeticholic Acid Theraapy Improves Histological Endpoints in Patients with Primary Biliary Cholangitis","volume":"18","author":"Bowlus","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jceh.2021.08.017","article-title":"Current Understanding of Bile Acids in Chronic Liver Disease","volume":"12","author":"Farooqui","year":"2022","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"111678","DOI":"10.1016\/j.mce.2022.111678","article-title":"Recent advances on FXR-targeting therapeutics","volume":"552","author":"Panzitt","year":"2022","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Mazzetti, M., Marconi, G., Mancinelli, M., Benedetti, A., Marzioni, M., and Maroni, L. (2021). The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities. J. Clin. Med., 10.","DOI":"10.3390\/jcm10081763"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1006\/bbrc.1993.1163","article-title":"Molecular cloning of a novel putative G protein-coupled receptor expressed in the cardiovascular system","volume":"190","author":"Okazaki","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6354","DOI":"10.1111\/febs.12446","article-title":"Sphingosine-1-phosphate receptor 2","volume":"280","author":"Adada","year":"2013","journal-title":"FEBS J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/hep.24681","article-title":"Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes","volume":"55","author":"Studer","year":"2012","journal-title":"Hepatology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/hep.27592","article-title":"Conjugated bile acid-activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression","volume":"61","author":"Nagahashi","year":"2015","journal-title":"Hepatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/hep.27085","article-title":"Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2","volume":"60","author":"Liu","year":"2014","journal-title":"Hepatology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"30988","DOI":"10.1074\/jbc.M115.668277","article-title":"Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line","volume":"290","author":"Liu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3389\/fimmu.2020.01149","article-title":"Macrophage Sphingosine 1-Phosphate Receptor 2 Blockade Attenuates Liver Inflammation and Fibrogenesis Triggered by NLRP3 Inflammasome","volume":"11","author":"Hou","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1011378","DOI":"10.3389\/fcimb.2022.1011378","article-title":"Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2","volume":"12","author":"Liu","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1172\/JCI119655","article-title":"Role and mechanisms of action of acetylcholine in the regulation of rat cholangiocyte secretory functions","volume":"100","author":"Alvaro","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0016-5085(99)70567-6","article-title":"Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats","volume":"117","author":"LeSage","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"E68","DOI":"10.1111\/hepr.12928","article-title":"Genetic loss of the muscarinic M(3) receptor markedly alters bile formation and cholestatic liver injury in mice","volume":"48","author":"Durchschein","year":"2018","journal-title":"Hepatol Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/lt.21361","article-title":"Ischemic cholangiopathy following liver transplantation from donation after cardiac death donors","volume":"14","author":"Chan","year":"2008","journal-title":"Liver Transpl."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1053\/jhep.2003.50176","article-title":"The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells","volume":"37","author":"Demers","year":"2003","journal-title":"Hepatology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.cell.2013.03.028","article-title":"A vitamin D receptor\/SMAD genomic circuit gates hepatic fibrotic response","volume":"153","author":"Ding","year":"2013","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1126\/science.1070477","article-title":"Vitamin D receptor as an intestinal bile acid sensor","volume":"296","author":"Makishima","year":"2002","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1002\/hep.26453","article-title":"Vitamin D nuclear receptor deficiency promotes cholestatic liver injury by disruption of biliary epithelial cell junctions in mice","volume":"58","author":"Firrincieli","year":"2013","journal-title":"Hepatology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"166067","DOI":"10.1016\/j.bbadis.2020.166067","article-title":"Cholangiopathy aggravation is caused by VDR ablation and alleviated by VDR-independent vitamin D signaling in ABCB4 knockout mice","volume":"1867","author":"Jager","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_97","first-page":"602321","article-title":"The role of vitamin d in primary biliary cirrhosis: Possible genetic and cell signaling mechanisms","volume":"2013","author":"Nguyen","year":"2013","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ebadi, M., Ip, S., Lytvyak, E., Asghari, S., Rider, E., Mason, A., and Montano-Loza, A.J. (2022). Vitamin D Is Associated with Clinical Outcomes in Patients with Primary Biliary Cholangitis. Nutrients, 14.","DOI":"10.3390\/nu14040878"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/00004836-199504000-00011","article-title":"Serum lipid and fat-soluble vitamin levels in primary sclerosing cholangitis","volume":"20","author":"Jorgensen","year":"1995","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Kempinska-Podhorodecka, A., Milkiewicz, M., Wasik, U., Ligocka, J., Zawadzki, M., Krawczyk, M., and Milkiewicz, P. (2017). Decreased Expression of Vitamin D Receptor Affects an Immune Response in Primary Biliary Cholangitis via the VDR-miRNA155-SOCS1 Pathway. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020289"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1053\/jhep.2002.30084","article-title":"Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis","volume":"35","author":"Vogel","year":"2002","journal-title":"Hepatology"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Kempi\u0144ska-Podhorodecka, A., Milkiewicz, M., Jab\u0142onski, D., Milkiewicz, P., and Wunsch, E. (2017). ApaI polymorphism of vitamin D receptor affects health-related quality of life in patients with primary sclerosing cholangitis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176264"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Sayaf, K., Zanotto, I., Russo, F.P., Gabbia, D., and De Martin, S. (2021). The Nuclear Receptor PXR in Chronic Liver Disease. Cells, 11.","DOI":"10.3390\/cells11010061"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.molmed.2021.12.006","article-title":"Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation","volume":"28","author":"Thibaut","year":"2022","journal-title":"Trends Mol. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1073\/pnas.051551698","article-title":"The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity","volume":"98","author":"Staudinger","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1073\/pnas.0438010100","article-title":"Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor","volume":"100","author":"Xie","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/164_2019_236","article-title":"Bile Acid-Activated Receptors: A Review on FXR and Other Nuclear Receptors","volume":"256","author":"Shin","year":"2019","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"45062","DOI":"10.1074\/jbc.M307145200","article-title":"Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity","volume":"278","author":"Guo","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"49517","DOI":"10.1074\/jbc.M409041200","article-title":"The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity","volume":"279","author":"Zhang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"571353","DOI":"10.1155\/2015\/571353","article-title":"Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR","volume":"2015","author":"Wunsch","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1146\/annurev-pharmtox-010919-023711","article-title":"(Inverse) Agonists of Retinoic Acid-Related Orphan Receptor gamma: Regulation of Immune Responses, Inflammation, and Autoimmune Disease","volume":"60","author":"Jetten","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1016\/j.ajpath.2020.07.010","article-title":"Retinoid-Related Orphan Receptor RORgammat in CD4(+) T-Cell-Mediated Intestinal Homeostasis and Inflammation","volume":"190","author":"Mickael","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-019-1785-z","article-title":"Bile acid metabolites control T(H)17 and T(reg) cell differentiation","volume":"576","author":"Hang","year":"2019","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41586-019-1865-0","article-title":"Microbial bile acid metabolites modulate gut RORgamma(+) regulatory T cell homeostasis","volume":"577","author":"Song","year":"2020","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.4049\/jimmunol.1203013","article-title":"IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation","volume":"191","author":"Tan","year":"2013","journal-title":"J. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"418","DOI":"10.5604\/16652681.1198820","article-title":"Liver fibrosis in bile duct-ligated rats correlates with increased hepatic IL-17 and TGF-beta2 expression","volume":"15","year":"2016","journal-title":"Ann. Hepatol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1002\/jcb.25776","article-title":"RAR-Related Orphan Receptor Gamma (ROR-gamma) Mediates Epithelial-Mesenchymal Transition of Hepatocytes During Hepatic Fibrosis","volume":"118","author":"Kim","year":"2017","journal-title":"J. Cell Biochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"725390","DOI":"10.3389\/fmed.2021.725390","article-title":"Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases","volume":"8","author":"Bruneau","year":"2021","journal-title":"Front. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jhep.2015.04.030","article-title":"Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4","volume":"63","author":"Out","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.27927","article-title":"Absence of the intestinal microbiota exacerbates hepatobiliary disease in a murine model of primary sclerosing cholangitis","volume":"63","author":"Tabibian","year":"2016","journal-title":"Hepatology"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Awoniyi, M., Wang, J., Ngo, B., Meadows, V., Tam, J., Viswanathan, A., Lai, Y., Montgomery, S., Farmer, M., and Kummen, M. (2022). Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC. Gut.","DOI":"10.1101\/2021.10.31.466701"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/s42255-021-00452-1","article-title":"Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling","volume":"3","author":"Schneider","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.jhep.2016.09.020","article-title":"The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation","volume":"66","author":"Schrumpf","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41564-018-0333-1","article-title":"Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis","volume":"4","author":"Nakamoto","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Zigmond, E., Zecher, B.F., Bartels, A.-L., Ziv-Baran, T., R\u00f6sch, T., Schachschal, G., Lohse, A.W., Ehlken, H., and Schramm, C. (2022). Bile Duct Colonization with Enterococcus sp. Associates with Disease Progression in Primary Sclerosing Cholangitis. Clin. Gastroenterol. Hepatol.","DOI":"10.1016\/j.cgh.2022.09.006"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1136\/gutjnl-2018-316670","article-title":"Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis","volume":"68","author":"Liao","year":"2019","journal-title":"Gut"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1080\/19490976.2020.1732268","article-title":"The microbiome modulating activity of bile acids","volume":"11","author":"Tian","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1055\/s-0037-1603324","article-title":"Epigenetics in the Primary Biliary Cholangitis and Primary Sclerosing Cholangitis","volume":"37","author":"Cheung","year":"2017","journal-title":"Semin. Liver Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s11938-019-00239-0","article-title":"Epigenetic Mechanisms of Pancreatobiliary Fibrosis","volume":"17","author":"Aseem","year":"2019","journal-title":"Curr. Treat. Options Gastroenterol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.mce.2012.04.008","article-title":"Epigenomic regulation of bile acid metabolism: Emerging role of transcriptional cofactors","volume":"368","author":"Smith","year":"2013","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/hep.27578","article-title":"Crucial roles of mixed-lineage leukemia 3 and 4 as epigenetic switches of the hepatic circadian clock controlling bile acid homeostasis in mice","volume":"61","author":"Kim","year":"2015","journal-title":"Hepatology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.livres.2017.03.002","article-title":"Bile acids as global regulators of hepatic nutrient metabolism","volume":"1","author":"Hylemon","year":"2017","journal-title":"Liver Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1210\/me.2009-0099","article-title":"ASCOM controls farnesoid X receptor transactivation through its associated histone H3 lysine 4 methyltransferase activity","volume":"23","author":"Kim","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"G771","DOI":"10.1152\/ajpgi.00499.2010","article-title":"Histone H3K4 trimethylation by MLL3 as part of ASCOM complex is critical for NR activation of bile acid transporter genes and is downregulated in cholestasis","volume":"300","author":"Ananthanarayanan","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1002\/hep.30966","article-title":"MicroRNA-210 Promotes Bile Acid-Induced Cholestatic Liver Injury by Targeting Mixed-Lineage Leukemia-4 Methyltransferase in Mice","volume":"71","author":"Kim","year":"2020","journal-title":"Hepatology"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Ostrycharz, E., Wasik, U., Kempinska-Podhorodecka, A., Banales, J.M., Milkiewicz, P., and Milkiewicz, M. (2020). Melatonin Protects Cholangiocytes from Oxidative Stress-Induced Proapoptotic and Proinflammatory Stimuli via miR-132 and miR-34. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249667"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Gerussi, A., Paraboschi, E.M., Cappadona, C., Caime, C., Binatti, E., Cristoferi, L., Asselta, R., and Invernizzi, P. (2022). The Role of Epigenetics in Primary Biliary Cholangitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094873"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12328-017-0799-z","article-title":"Genetics and epigenetics in the pathogenesis of primary biliary cholangitis","volume":"11","author":"Joshita","year":"2018","journal-title":"Clin. J. Gastroenterol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.2217\/epi-2020-0048","article-title":"Genome-wide resolution peripheral blood methylome profiling reveals signatures for cholestatic liver disease","volume":"12","author":"Moore","year":"2020","journal-title":"Epigenomics"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/hep4.1809","article-title":"Induced Pluripotent Stem Cells from Subjects with Primary Sclerosing Cholangitis Develop a Senescence Phenotype Following Biliary Differentiation","volume":"6","author":"Hamdan","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1053\/j.gastro.2020.10.008","article-title":"Epigenomic Evaluation of Cholangiocyte Transforming Growth Factor-beta Signaling Identifies a Selective Role for Histone 3 Lysine 9 Acetylation in Biliary Fibrosis","volume":"160","author":"Aseem","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.jhep.2021.12.014","article-title":"Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300\/ELK1 complex","volume":"76","author":"Sehrawat","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1074\/jbc.M117.777409","article-title":"ETS Proto-oncogene 1 Transcriptionally Up-regulates the Cholangiocyte Senescence-associated Protein Cyclin-dependent Kinase Inhibitor 2A","volume":"292","author":"Splinter","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1002\/hep.30706","article-title":"Proteasomal Degradation of Enhancer of Zeste Homologue 2 in Cholangiocytes Promotes Biliary Fibrosis","volume":"70","author":"Shi","year":"2019","journal-title":"Hepatology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/hep.29145","article-title":"The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice","volume":"66","author":"Li","year":"2017","journal-title":"Hepatology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.30662","article-title":"Cholangiocyte-Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis","volume":"70","author":"Liu","year":"2019","journal-title":"Hepatology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/hep.30698","article-title":"Long Noncoding RNA H19 Contributes to Cholangiocyte Proliferation and Cholestatic Liver Fibrosis in Biliary Atresia","volume":"70","author":"Xiao","year":"2019","journal-title":"Hepatology"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Li, X., Liu, R., Wang, Y., Zhu, W., Zhao, D., Wang, X., Yang, H., Gurley, E.C., Chen, W., and Hylemon, P.B. (2020). Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions. Cells, 9.","DOI":"10.3390\/cells9010190"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/5\/792\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:46:22Z","timestamp":1760121982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/5\/792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":148,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cells12050792"],"URL":"https:\/\/doi.org\/10.3390\/cells12050792","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,2]]}}}