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However, the exact relationship between the development of liver fibrosis and the progression of cholestatic liver disease remains elusive. Periductular fibroblasts located around the bile ducts seem biologically different from hepatic stellate cells (HSCs). The fibrotic events in these clinical conditions appear to be related to complex crosstalk between immune\/inflammatory mechanisms, cytokine signalling, and perturbed homeostasis between cholangiocytes and mesenchymal cells. Several animal models including bile duct ligation (BDL) and the Mdr2-knockout mice have improved our understanding of mechanisms underlying chronic cholestasis. In the present review, we aim to elucidate the mechanisms of fibrosis in order to help to identify potential diagnostic and therapeutic targets.<\/jats:p>","DOI":"10.3390\/cells10051107","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T11:06:01Z","timestamp":1620212761000},"page":"1107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Fibrotic Events in the Progression of Cholestatic Liver Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Hanghang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Immunology, Ophthalmology &amp; ENT, Complutense University School of Medicine, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5963-5295","authenticated-orcid":false,"given":"Chaobo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology &amp; ENT, Complutense University School of Medicine, 28040 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n (IiSGM), 28007 Madrid, Spain"},{"name":"Department of General Surgery, Wuxi Xishan People\u2019s Hospital, Wuxi 214000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siham","family":"Ziani","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology &amp; ENT, Complutense University School of Medicine, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4197-4843","authenticated-orcid":false,"given":"Leonard J.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering (IBioE), School of Engineering, Faraday Building, The University of Edinburgh, Edinburgh EH9 3 JL, Scotland, UK"},{"name":"Institute of Biological Chemistry, Biophysics and Bioengineering (IB3), School of Engineering and Physical Sciences (EPS), Heriot-Watt University, Edinburgh EH14 4AS, Scotland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-3557","authenticated-orcid":false,"given":"Mat\u00edas A.","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Hepatology Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"Centro de Investigacion Biomedica en Red, Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28029 Madrid, Spain"},{"name":"Instituto de Investigaciones Sanitarias de Navarra IdiSNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia A.","family":"Nevzorova","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology &amp; ENT, Complutense University School of Medicine, 28040 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n (IiSGM), 28007 Madrid, Spain"},{"name":"Centro de Investigacion Biomedica en Red, Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28029 Madrid, Spain"},{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-650X","authenticated-orcid":false,"given":"Francisco Javier","family":"Cubero","sequence":"additional","affiliation":[{"name":"Department of Immunology, Ophthalmology &amp; ENT, Complutense University School of Medicine, 28040 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n (IiSGM), 28007 Madrid, Spain"},{"name":"Centro de Investigacion Biomedica en Red, Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0168-8278(85)80012-X","article-title":"What is cholestasis in 1985?","volume":"1","author":"Erlinger","year":"1985","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fuchs, C.D., Halilbasic, E., and Trauner, M. (2020). Pathophysiologic basis for alternative therapies for cholestasis. Liver Biol. Pathobiol., 364\u2013377.","DOI":"10.1002\/9781119436812.ch30"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1002\/hep.29569","article-title":"A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis","volume":"67","author":"Kowdley","year":"2018","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo-controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ajg.2017.287","article-title":"Effects of bezafibrate on outcome and pruritus in primary biliary cholangitis with suboptimal ursodeoxycholic acid response","volume":"113","author":"Reig","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S1028","DOI":"10.1016\/S0016-5085(13)63825-1","article-title":"Fenofibrate improves alkaline phosphatase in primary sclerosing cholangitis","volume":"144","author":"Dejman","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1097\/MCG.0b013e3181662426","article-title":"A double-blind, placebo-controlled, randomized study of infliximab in primary sclerosing cholangitis","volume":"42","author":"Hommes","year":"2008","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/hep.28359","article-title":"Ustekinumab for patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid: A proof-of-concept study","volume":"64","author":"Hirschfield","year":"2016","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1756284818787400","DOI":"10.1177\/1756284818787400","article-title":"Cholestatic liver diseases: New targets, new therapies","volume":"11","author":"Santiago","year":"2018","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cai, S.Y., Li, M., and Boyer, J.L. (2020). The role of bile acid-mediated inflammation in cholestatic liver injury. Liver Biol. Pathobiol., 728\u2013736.","DOI":"10.1002\/9781119436812.ch56"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cld.2018.06.003","article-title":"Progressive familial intrahepatic cholestasis","volume":"22","author":"Bull","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2007.11.010","article-title":"Mechanisms of cholestasis","volume":"12","author":"Zollner","year":"2008","journal-title":"Clin. Liver Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1038\/ncomms3823","article-title":"Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology","volume":"4","author":"Mederacke","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.biocel.2009.07.020","article-title":"Biliary differentiation and bile duct morphogenesis in development and disease","volume":"43","author":"Raynaud","year":"2011","journal-title":"Int. J. Biochem Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/liv.13698","article-title":"Cenicriviroc, a cytokine receptor antagonist, potentiates all-trans retinoic acid in reducing liver injury in cholestatic rodents","volume":"38","author":"Yu","year":"2018","journal-title":"Liver Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1042\/CS20181123","article-title":"Immunological abnormalities in patients with primary biliary cholangitis","volume":"133","author":"Ma","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1053\/j.gastro.2012.12.005","article-title":"Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid","volume":"144","author":"Carbone","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2014.08.029","article-title":"Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: An international follow-up study","volume":"147","author":"Lammers","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1136\/gutjnl-2014-308351","article-title":"Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: A multicentre international study","volume":"65","author":"Trivedi","year":"2016","journal-title":"Gut"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). Electronic address, e.e.e.; European Association for the Study of the, L. Easl clinical practice guidelines: The diagnosis and management of patients with primary biliary cholangitis. J. Hepatol., 67, 145\u2013172.","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41575-019-0226-7","article-title":"Primary biliary cholangitis: Pathogenesis and therapeutic opportunities","volume":"17","author":"Gulamhusein","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1053\/j.gastro.2015.08.031","article-title":"Changing nomenclature for pbc: From \u2018cirrhosis\u2019 to \u2018cholangitis\u2019","volume":"149","author":"Beuers","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJMra043898","article-title":"Primary biliary cirrhosis","volume":"353","author":"Kaplan","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/apt.13794","article-title":"The inter-relationship of symptom severity and quality of life in 2055 patients with primary biliary cholangitis","volume":"44","author":"Dyson","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/hep.26365","article-title":"Impact of primary biliary cirrhosis on perceived quality of life: The uk-pbc national study","volume":"58","author":"Mells","year":"2013","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, T., and Chiang, J.Y. (2020). Bile acid metabolism in health and disease: An update. Liver Biol. Pathobiol., 269\u2013285.","DOI":"10.1002\/9781119436812.ch23"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.path.2018.02.010","article-title":"Primary biliary cholangitis and autoimmune hepatitis","volume":"11","author":"Gonzalez","year":"2018","journal-title":"Surg. Pathol. Clin."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1111\/liv.12434","article-title":"Rising incidence and prevalence of primary biliary cirrhosis: A large population-based study","volume":"34","author":"Boonstra","year":"2014","journal-title":"Liver Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/hep.28859","article-title":"Large-scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis","volume":"65","author":"Dahlqvist","year":"2017","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1055\/s-0034-1383730","article-title":"The new epidemiology of primary biliary cirrhosis","volume":"34","author":"Griffiths","year":"2014","journal-title":"Semin. Liver Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.cgh.2017.12.033","article-title":"Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment","volume":"16","author":"Lu","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1055\/s-0035-1567831","article-title":"Genome-wide association studies in primary biliary cirrhosis","volume":"35","author":"Gulamhusein","year":"2015","journal-title":"Semin. Liver Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cld.2015.08.002","article-title":"The immunogenetics of autoimmune cholestasis","volume":"20","author":"Trivedi","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jhep.2010.02.019","article-title":"Demographic, lifestyle, medical and familial factors associated with primary biliary cirrhosis","volume":"53","author":"Corpechot","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1002\/hep.20907","article-title":"Risk factors and comorbidities in primary biliary cirrhosis: A controlled interview-based study of 1032 patients","volume":"42","author":"Gershwin","year":"2005","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1136\/gut.24.10.940","article-title":"Primary biliary cirrhosis: Geographical clustering and symptomatic onset seasonality","volume":"24","author":"Hamlyn","year":"1983","journal-title":"Gut"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/hep.24414","article-title":"Human leukocyte antigen in primary biliary cirrhosis: An old story now reviving","volume":"54","author":"Invernizzi","year":"2011","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1055\/s-0034-1383726","article-title":"Environmental factors in primary biliary cirrhosis","volume":"34","author":"Juran","year":"2014","journal-title":"Semin. Liver Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jhep.2018.06.027","article-title":"Identification of a xenobiotic as a potential environmental trigger in primary biliary cholangitis","volume":"69","author":"Probert","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/cei.12224","article-title":"Escherichia coli infection induces autoimmune cholangitis and anti-mitochondrial antibodies in non-obese diabetic (nod).B6 (idd10\/idd18) mice","volume":"175","author":"Wang","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/hep.26702","article-title":"Cd8 t cells primed in the gut-associated lymphoid tissue induce immune-mediated cholangitis in mice","volume":"59","author":"Seidel","year":"2014","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.autrev.2017.07.002","article-title":"Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases","volume":"16","author":"Li","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S0140-6736(02)07374-9","article-title":"Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease","volume":"359","author":"Grant","year":"2002","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.autrev.2015.08.009","article-title":"The critical role of toll-like receptors--from microbial recognition to autoimmunity: A comprehensive review","volume":"15","author":"Gerswhin","year":"2016","journal-title":"Autoimmun. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1053\/gast.2002.36027","article-title":"Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: Follow-up for up to 28 years","volume":"123","author":"Prince","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/0016-5085(85)90213-6","article-title":"Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial","volume":"89","author":"Christensen","year":"1985","journal-title":"Gastroenterology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/hep.510260508","article-title":"Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes","volume":"26","author":"Jones","year":"1997","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1016\/S0140-6736(18)30300-3","article-title":"Primary sclerosing cholangitis","volume":"391","author":"Dyson","year":"2018","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1002\/hep.26565","article-title":"Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis","volume":"58","author":"Boonstra","year":"2013","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/S0168-8278(05)80618-X","article-title":"Risk factors in primary sclerosing cholangitis","volume":"21","author":"Schrumpf","year":"1994","journal-title":"J. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1572-0241.2006.00872.x","article-title":"Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: A single center study","volume":"102","author":"Tischendorf","year":"2007","journal-title":"Am. J. Gastroenterol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000440705","article-title":"Worldwide incidence of autoimmune liver disease","volume":"33","author":"Jepsen","year":"2015","journal-title":"Dig. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1002\/hep.24247","article-title":"Incidence of primary sclerosing cholangitis: A systematic review and meta-analysis","volume":"53","author":"Molodecky","year":"2011","journal-title":"Hepatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.gastro.2003.07.011","article-title":"Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a united states community","volume":"125","author":"Bambha","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0168-8278(94)80240-8","article-title":"Epidemiology of primary sclerosing cholangitis in spain. Spanish association for the study of the liver","volume":"21","author":"Escorsell","year":"1994","journal-title":"J. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/hep.23678","article-title":"Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in sweden","volume":"52","author":"Lindkvist","year":"2010","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/ng.2616","article-title":"Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis","volume":"45","author":"Liu","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng.3745","article-title":"Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease","volume":"49","author":"Ji","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.3748\/wjg.v21.i6.1956","article-title":"Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis","volume":"21","author":"Janse","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/hep.26447","article-title":"Increased t helper type 17 response to pathogen stimulation in patients with primary sclerosing cholangitis","volume":"58","author":"Katt","year":"2013","journal-title":"Hepatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1136\/gutjnl-2015-311004","article-title":"Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from ibd","volume":"65","author":"Sabino","year":"2016","journal-title":"Gut"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/hep.1840100406","article-title":"Primary sclerosing cholangitis: Natural history, prognostic factors and survival analysis","volume":"10","author":"Wiesner","year":"1989","journal-title":"Hepatology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1148\/radiol.2263011623","article-title":"Mr imaging features of primary sclerosing cholangitis: Patterns of cirrhosis in relationship to clinical severity of disease","volume":"226","author":"Bader","year":"2003","journal-title":"Radiology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/j.1572-0241.2004.04106.x","article-title":"Dominant strictures in patients with primary sclerosing cholangitis","volume":"99","author":"Bjornsson","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_67","first-page":"1404","article-title":"Primary sclerosing cholangitis and ulcerative colitis: Evidence for increased neoplastic potential","volume":"22","author":"Broome","year":"1995","journal-title":"Hepatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/hep.23294","article-title":"Diagnosis and management of primary sclerosing cholangitis","volume":"51","author":"Chapman","year":"2010","journal-title":"Hepatology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jhep.2008.08.013","article-title":"High lifetime risk of cancer in primary sclerosing cholangitis","volume":"50","author":"Claessen","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jhep.2009.04.009","article-title":"Easl clinical practice guidelines: Management of cholestatic liver diseases","volume":"51","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_71","first-page":"387","article-title":"Endoscopic therapy in primary sclerosing cholangitis: Outcome of treatment and risk of cancer","volume":"48","author":"Linder","year":"2001","journal-title":"Hepatogastroenterology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0168-8278(01)00288-4","article-title":"Hepatic and extrahepatic malignancies in primary sclerosing cholangitis","volume":"36","author":"Bergquist","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1080\/003655202760373434","article-title":"Cholangiocarcinoma in primary sclerosing cholangitis: Risk factors and clinical presentation","volume":"37","author":"Boberg","year":"2002","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1478-3231.2011.02575.x","article-title":"Malignancies and mortality in 200 patients with primary sclerosering cholangitis: A long-term single-centre study","volume":"32","author":"Fevery","year":"2012","journal-title":"Liver Int."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1053\/j.gastro.2011.06.049","article-title":"Embryonic ductal plate cells give rise to cholangiocytes, periportal hepatocytes, and adult liver progenitor cells","volume":"141","author":"Carpentier","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/cphy.c120027","article-title":"Bile formation and secretion","volume":"3","author":"Boyer","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/hep.31067","article-title":"The spectrum of reactive cholangiocytes in primary sclerosing cholangitis","volume":"71","author":"Guicciardi","year":"2020","journal-title":"Hepatology"},{"key":"ref_79","first-page":"250","article-title":"General and specific aspects of experimental dose measurement in total body irradiation (tbi)","volume":"162","author":"Jensen","year":"1986","journal-title":"Strahlenther. Onkol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ydbio.2015.05.012","article-title":"Transcription factors sox4 and sox9 cooperatively control development of bile ducts","volume":"404","author":"Poncy","year":"2015","journal-title":"Dev. Biol."},{"key":"ref_81","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_82","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1002\/hep.23405","article-title":"Portal fibroblasts: Underappreciated mediators of biliary fibrosis","volume":"51","author":"Dranoff","year":"2010","journal-title":"Hepatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"9448","DOI":"10.1073\/pnas.1201840109","article-title":"Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis","volume":"109","author":"Kisseleva","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"E3297","DOI":"10.1073\/pnas.1400062111","article-title":"Origin of myofibroblasts in the fibrotic liver in mice","volume":"111","author":"Iwaisako","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Chen, Y., Gilbert, M.A., Grochowski, C.M., McEldrew, D., Llewellyn, J., Waisbourd-Zinman, O., Hakonarson, H., Bailey-Wilson, J.E., Russo, P., and Wells, R.G. (2018). A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene efemp1. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007532"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/hep.27653","article-title":"Beyond scar formation: Portal myofibroblast-mediated angiogenesis in the fibrotic liver","volume":"61","author":"Fausther","year":"2015","journal-title":"Hepatology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1172\/JCI88845","article-title":"Mesothelin\/mucin 16 signaling in activated portal fibroblasts regulates cholestatic liver fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.jhep.2019.04.012","article-title":"Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in mdr2 knockout mice","volume":"71","author":"Nishio","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1053\/j.gastro.2014.05.001","article-title":"The portal fibroblast: Not just a poor man\u2019s stellate cell","volume":"147","author":"Wells","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fphar.2014.00167","article-title":"The types of hepatic myofibroblasts contributing to liver fibrosis of different etiologies","volume":"5","author":"Xu","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1046\/j.0106-9543.2002.01674.x","article-title":"The correlation between portal myofibroblasts and development of intrahepatic bile ducts and arterial branches in human liver","volume":"22","author":"Libbrecht","year":"2002","journal-title":"Liver"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.semcdb.2017.07.001","article-title":"Probing the unseen structure and function of liver cells through atomic force microscopy","volume":"73","author":"Braet","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_94","first-page":"409","article-title":"Ultrastructure and function of kupffer cells and other sinusoidal cells in the liver","volume":"6","author":"Wisse","year":"1977","journal-title":"Med. Chir. Digest."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"27398","DOI":"10.1038\/srep27398","article-title":"The alterations in the extracellular matrix composition guide the repair of damaged liver tissue","volume":"6","author":"Klaas","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"C789","DOI":"10.1152\/ajpcell.00230.2013","article-title":"Cellular mechanisms of tissue fibrosis. 5. Novel insights into liver fibrosis","volume":"305","author":"Mallat","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1053\/j.gastro.2011.09.049","article-title":"A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells","volume":"142","author":"Teratani","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jhep.2018.03.011","article-title":"A simple diet- and chemical-induced murine nash model with rapid progression of steatohepatitis, fibrosis and liver cancer","volume":"69","author":"Tsuchida","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/hepr.13040","article-title":"Vitamin a-coupled liposome system targeting free cholesterol accumulation in hepatic stellate cells offers a beneficial therapeutic strategy for liver fibrosis","volume":"48","author":"Furuhashi","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1476-5926-8-5","article-title":"Immunohistochemical study of the phenotypic change of the mesenchymal cells during portal tract maturation in normal and fibrous (ductal plate malformation) fetal liver","volume":"8","author":"Villeneuve","year":"2009","journal-title":"Comp. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1053\/j.gastro.2008.03.075","article-title":"P75 neurotrophin receptor is a marker for precursors of stellate cells and portal fibroblasts in mouse fetal liver","volume":"135","author":"Suzuki","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/hep.22721","article-title":"Mesenchymal origin of hepatic stellate cells, submesothelial cells, and perivascular mesenchymal cells during mouse liver development","volume":"49","author":"Asahina","year":"2009","journal-title":"Hepatology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1002\/hep.23184","article-title":"The niche of stellate cells within rat liver","volume":"50","author":"Sawitza","year":"2009","journal-title":"Hepatology"},{"key":"ref_105","first-page":"4130","article-title":"Myofibroblastic transformation of rat hepatic stellate cells: The role of notch signaling and epithelial-mesenchymal transition regulation","volume":"19","author":"Zhang","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1136\/gut.2009.188367","article-title":"Characterisation of the liver progenitor cell niche in liver diseases: Potential involvement of wnt and notch signalling","volume":"59","author":"Spee","year":"2010","journal-title":"Gut"},{"key":"ref_107","first-page":"769","article-title":"Resveratrol can prevent ccl(4)-induced liver injury by inhibiting notch signaling pathway","volume":"31","author":"Tanriverdi","year":"2016","journal-title":"Histol. Histopathol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Chen, Y., Zheng, S., Qi, D., Zheng, S., Guo, J., Zhang, S., and Weng, Z. (2012). Inhibition of notch signaling by a gamma-secretase inhibitor attenuates hepatic fibrosis in rats. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046512"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Adams, J.M., and Jafar-Nejad, H. (2019). The roles of notch signaling in liver development and disease. Biomolecules, 9.","DOI":"10.3390\/biom9100608"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41467-017-00204-4","article-title":"The liver-enriched lnc-lfar1 promotes liver fibrosis by activating tgfbeta and notch pathways","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.lfs.2017.11.018","article-title":"Tgf-beta1 signaling regulates mouse hepatic stellate cell differentiation via the jagged1\/notch pathway","volume":"192","author":"Aimaiti","year":"2018","journal-title":"Life Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20071570","article-title":"Liver fibrosis","volume":"411","author":"Wallace","year":"2008","journal-title":"Biochem. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in tissue repair, regeneration, and fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1136\/gutjnl-2019-319091","article-title":"Tgf-beta2 silencing to target biliary-derived liver diseases","volume":"69","author":"Dropmann","year":"2020","journal-title":"Gut"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.15252\/emmm.201707860","article-title":"Sox9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis","volume":"9","author":"Athwal","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/hep.29834","article-title":"Endothelial notch activation reshapes the angiocrine of sinusoidal endothelia to aggravate liver fibrosis and blunt regeneration in mice","volume":"68","author":"Duan","year":"2018","journal-title":"Hepatology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"eaat0344","DOI":"10.1126\/scitranslmed.aat0344","article-title":"Hepatocyte notch activation induces liver fibrosis in nonalcoholic steatohepatitis","volume":"10","author":"Zhu","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"G102","DOI":"10.1152\/ajpgi.00452.2016","article-title":"Emerging concepts in biliary repair and fibrosis","volume":"313","author":"Fabris","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.stem.2019.04.005","article-title":"Yap, but not rspo-lgr4\/5, signaling in biliary epithelial cells promotes a ductular reaction in response to liver injury","volume":"25","author":"Sun","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/cdd.2017.163","article-title":"P53 shades of hippo","volume":"25","author":"Furth","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6542","DOI":"10.1073\/pnas.1302168110","article-title":"Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated tweak signaling","volume":"110","author":"Bird","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1172\/JCI23486","article-title":"Tweak induces liver progenitor cell proliferation","volume":"115","author":"Jakubowski","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.jhep.2017.10.017","article-title":"Hedgehog signalling in liver pathophysiology","volume":"68","author":"Machado","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1053\/j.gastro.2012.10.025","article-title":"Notch signaling in hepatocellular carcinoma: Guilty in association!","volume":"143","author":"Strazzabosco","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_125","first-page":"3331","article-title":"Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans","volume":"118","author":"Omenetti","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1002\/hep.26511","article-title":"Cross-talk between notch and hedgehog regulates hepatic stellate cell fate in mice","volume":"58","author":"Xie","year":"2013","journal-title":"Hepatology"},{"key":"ref_127","first-page":"2291","article-title":"A conserved role for notch signaling in priming the cellular response to shh through ciliary localisation of the key shh transducer smo","volume":"142","author":"Stasiulewicz","year":"2015","journal-title":"Development"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/hep.27394","article-title":"Myeloid-specific disruption of recombination signal binding protein jkappa ameliorates hepatic fibrosis by attenuating inflammation through cylindromatosis in mice","volume":"61","author":"He","year":"2015","journal-title":"Hepatology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1172\/JCI93557","article-title":"Extracellular matrix as a driver of progressive fibrosis","volume":"128","author":"Herrera","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1053\/j.gastro.2015.02.056","article-title":"Beta-catenin signaling and roles in liver homeostasis, injury, and tumorigenesis","volume":"148","author":"Monga","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.jhep.2016.11.004","article-title":"Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating sirtuin 1 expression","volume":"66","author":"Ramirez","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.matbio.2017.12.012","article-title":"Matrix metalloproteinases and liver fibrosis (translational aspects)","volume":"68-69","author":"Roeb","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"G219","DOI":"10.1152\/ajpgi.00160.2016","article-title":"Wnt-5a regulates tgf-beta-related activities in liver fibrosis","volume":"312","author":"Beljaars","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Carpino, G., Nobili, V., Renzi, A., De Stefanis, C., Stronati, L., Franchitto, A., Alisi, A., Onori, P., De Vito, R., and Alpini, G. (2016). Macrophage activation in pediatric nonalcoholic fatty liver disease (nafld) correlates with hepatic progenitor cell response via wnt3a pathway. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157246"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.3748\/wjg.v22.i6.2092","article-title":"Human urokinase-type plasminogen activator gene-modified bone marrow-derived mesenchymal stem cells attenuate liver fibrosis in rats by down-regulating the wnt signaling pathway","volume":"22","author":"Ma","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.3748\/wjg.v18.i15.1745","article-title":"Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays","volume":"18","author":"Xiong","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"G39","DOI":"10.1152\/ajpgi.00263.2007","article-title":"Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis","volume":"294","author":"Cheng","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1053\/j.gastro.2017.01.021","article-title":"Stearoyl-coa desaturase promotes liver fibrosis and tumor development in mice via a wnt positive-signaling loop by stabilization of low-density lipoprotein-receptor-related proteins 5 and 6","volume":"152","author":"Lai","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.gene.2018.06.053","article-title":"Emerging role and therapeutic implication of wnt signaling pathways in liver fibrosis","volume":"674","author":"Wang","year":"2018","journal-title":"Gene"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1002\/hep.30927","article-title":"Wnt\/beta-catenin signaling plays a protective role in the mdr2 knockout murine model of cholestatic liver disease","volume":"71","author":"Kosar","year":"2020","journal-title":"Hepatology"},{"key":"ref_141","first-page":"F85","article-title":"Regulation and function of the jnk subgroup of map kinases","volume":"1333","author":"Minden","year":"1997","journal-title":"Biochim Biophys Acta"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ceb.2007.02.001","article-title":"The jnk signal transduction pathway","volume":"19","author":"Weston","year":"2007","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1136\/gutjnl-2013-305507","article-title":"Jnk1 in murine hepatic stellate cells is a crucial mediator of liver fibrogenesis","volume":"63","author":"Zhao","year":"2014","journal-title":"Gut"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1053\/j.gastro.2009.09.015","article-title":"Modulation of hepatic fibrosis by c-jun-n-terminal kinase inhibition","volume":"138","author":"Kluwe","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1515\/BC.2009.111","article-title":"Mechanisms of liver disease: Cross-talk between the nf-kappab and jnk pathways","volume":"390","author":"Papa","year":"2009","journal-title":"Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1242\/jeb.029454","article-title":"Molecular physiology and genetics of na+-independent slc4 anion exchangers","volume":"212","author":"Alper","year":"2009","journal-title":"J. Exp. Biol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.jhep.2020.10.010","article-title":"Hepatobiliary acid-base homeostasis: Insights from analogous secretory epithelia","volume":"74","author":"Trampert","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/0016-5085(93)90735-U","article-title":"Abnormal expression of anion exchanger genes in primary biliary cirrhosis","volume":"105","author":"Prieto","year":"1993","journal-title":"Gastroenterology"},{"key":"ref_149","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_150","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1053\/jhep.2002.33634","article-title":"Defective regulation of cholangiocyte cl-\/hco3(-) and na+\/h+ exchanger activities in primary biliary cirrhosis","volume":"35","author":"Melero","year":"2002","journal-title":"Hepatology"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1053\/j.gastro.2008.02.020","article-title":"Ae2a,b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis","volume":"134","author":"Salas","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"921","DOI":"10.2174\/1389450116666151019102358","article-title":"Cell death and micrornas in cholestatic liver diseases: Update on potential therapeutic applications","volume":"18","author":"Castro","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/hep.29533","article-title":"Microrna-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation","volume":"67","author":"Erice","year":"2018","journal-title":"Hepatology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nrgastro.2015.12","article-title":"Novel therapeutic targets in primary biliary cirrhosis","volume":"12","author":"Dyson","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jaut.2009.02.022","article-title":"Primary biliary cirrhosis is associated with altered hepatic microrna expression","volume":"32","author":"Padgett","year":"2009","journal-title":"J. Autoimmun."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2007.08.020","article-title":"Cyclic amp regulates bicarbonate secretion in cholangiocytes through release of atp into bile","volume":"133","author":"Minagawa","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/hep.25691","article-title":"Up-regulation of microrna 506 leads to decreased cl-\/hco3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis","volume":"56","author":"Banales","year":"2012","journal-title":"Hepatology"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3748\/wjg.15.804","article-title":"Bile acids: Chemistry, physiology, and pathophysiology","volume":"15","author":"Monte","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1194\/jlr.M004531","article-title":"A putative role of micro rna in regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes","volume":"51","author":"Song","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/emmm.201201228","article-title":"Mir-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity","volume":"4","author":"Allen","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/hep.26427","article-title":"Regulation of cholesterol and bile acid homeostasis by the cholesterol 7alpha-hydroxylase\/steroid response element-binding protein 2\/microrna-33a axis in mice","volume":"58","author":"Li","year":"2013","journal-title":"Hepatology"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/MOG.0000000000000051","article-title":"Micrornas and cholestatic liver diseases","volume":"30","author":"Marin","year":"2014","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bpg.2018.05.012","article-title":"Pathophysiology of primary biliary cholangitis","volume":"34\u201335","author":"Gulamhusein","year":"2018","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0140-6736(88)91894-6","article-title":"Primary biliary cirrhosis: Identification of two major m2 mitochondrial autoantigens","volume":"1","author":"Yeaman","year":"1988","journal-title":"Lancet"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1172\/JCI0214698","article-title":"Quantitative and functional analysis of pdc-e2-specific autoreactive cytotoxic t lymphocytes in primary biliary cirrhosis","volume":"109","author":"Kita","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1084\/jem.20010956","article-title":"Identification of hla-a2-restricted cd8(+) cytotoxic t cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes cross-presented by dendritic cells","volume":"195","author":"Kita","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/hep.23783","article-title":"Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis","volume":"52","author":"Lleo","year":"2010","journal-title":"Hepatology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/MOG.0000000000000507","article-title":"The genetics of primary biliary cholangitis","volume":"35","author":"Tanaka","year":"2019","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/ng.3528","article-title":"Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci","volume":"48","author":"Ellinghaus","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/ng.3176","article-title":"High-density mapping of the mhc identifies a shared role for hla-drb1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis","volume":"47","author":"Goyette","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1053\/j.gastro.2009.11.046","article-title":"Genome-wide association analysis in primary sclerosing cholangitis","volume":"138","author":"Karlsen","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jhep.2012.03.031","article-title":"Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci","volume":"57","author":"Folseraas","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/hep.23810","article-title":"The biliary hco(3)(-) umbrella: A unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies","volume":"52","author":"Beuers","year":"2010","journal-title":"Hepatology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1159\/000450916","article-title":"The role of inflammation in the mechanisms of bile acid-induced liver damage","volume":"35","author":"Cai","year":"2017","journal-title":"Dig. Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.bpg.2011.02.001","article-title":"Fibrosis in autoimmune and cholestatic liver disease","volume":"25","author":"Osterreicher","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1007\/s10354-008-0592-1","article-title":"Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases","volume":"158","author":"Trauner","year":"2008","journal-title":"Wien. Med. Wochenschr."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1053\/j.gastro.2004.04.009","article-title":"Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in mdr2 (abcb4) knockout mice","volume":"127","author":"Fickert","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/hep.20600","article-title":"Transdifferentiation of rat hepatocytes into biliary cells after bile duct ligation and toxic biliary injury","volume":"41","author":"Michalopoulos","year":"2005","journal-title":"Hepatology"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0002-9440(10)65034-1","article-title":"The development and compensation of biliary cirrhosis in interleukin-6-deficient mice","volume":"156","author":"Ezure","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/S0002-9440(10)64089-8","article-title":"Replicative senescence of biliary epithelial cells precedes bile duct loss in chronic liver allograft rejection: Increased expression of p21(waf1\/cip1) as a disease marker and the influence of immunosuppressive drugs","volume":"158","author":"Lunz","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/hep.1840200217","article-title":"Human biliary epithelial cells secrete and respond to cytokines and hepatocyte growth factors in vitro: Interleukin-6, hepatocyte growth factor and epidermal growth factor promote DNA synthesis in vitro","volume":"20","author":"Matsumoto","year":"1994","journal-title":"Hepatology"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.bbadis.2018.07.025","article-title":"Animal models of cholestasis: An update on inflammatory cholangiopathies","volume":"1865","author":"Mariotti","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S1074-7613(00)80170-3","article-title":"Abrogation of tgfbeta signaling in t cells leads to spontaneous t cell differentiation and autoimmune disease","volume":"12","author":"Gorelik","year":"2000","journal-title":"Immunity"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"6340","DOI":"10.4049\/jimmunol.1300397","article-title":"Truncated form of tgf-betarii, but not its absence, induces memory cd8+ t cell expansion and lymphoproliferative disorder in mice","volume":"190","author":"Ishigame","year":"2013","journal-title":"J. Immunol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.jhep.2004.08.002","article-title":"Liver autoimmune serology: A consensus statement from the committee for autoimmune serology of the international autoimmune hepatitis group","volume":"41","author":"Vergani","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/hep.510300145","article-title":"In situ nucleic acid detection of pdc-e2, bcoadc-e2, ogdc-e2, pdc-e1alpha, bcoadc-e1alpha, ogdc-e1, and the e3 binding protein (protein x) in primary biliary cirrhosis","volume":"30","author":"Harada","year":"1999","journal-title":"Hepatology"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3343\/alm.2019.39.3.291","article-title":"Detection of autoantibodies against nucleoporin p62 in sera of patients with primary biliary cholangitis","volume":"39","author":"Bauer","year":"2019","journal-title":"Ann. Lab. Med."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Bauer, A., Habior, A., Wieszczy, P., and Gawel, D. (2021). Analysis of autoantibodies against promyelocytic leukemia nuclear body components and biochemical parameters in sera of patients with primary biliary cholangitis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11040587"},{"key":"ref_189","unstructured":"Liu, Z.Y., Xu, L., and Liu, B. (2020). Detection of anti-kelch-like 12 and anti-hexokinase 1 antibodies in primary biliary cholangitis patients in china. Rev. Esp. Enferm. Dig."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cca.2009.06.035","article-title":"Autoantibodies to asialoglycoprotein receptor (asgpr) measured by a novel elisa--revival of a disease-activity marker in autoimmune hepatitis","volume":"408","author":"Hausdorf","year":"2009","journal-title":"Clin. Chim. Acta"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.14309\/ajg.0000000000000690","article-title":"Novel anti-hexokinase 1 antibodies are associated with poor prognosis in patients with primary biliary cholangitis","volume":"115","author":"Reig","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1053\/gast.2000.9366","article-title":"\u201cAtypical p-anca\u201d in ibd and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines","volume":"119","author":"Terjung","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/gutjnl-2016-311739","article-title":"Anti-gp2 iga autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis","volume":"66","author":"Jendrek","year":"2017","journal-title":"Gut"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1016\/j.jhep.2015.02.023","article-title":"New paradigms in the treatment of hepatic cholestasis: From udca to fxr, pxr and beyond","volume":"62","author":"Beuers","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/hep.23082","article-title":"High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis","volume":"50","author":"Lindor","year":"2009","journal-title":"Hepatology"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1056\/NEJM199405123301903","article-title":"Ursodiol for the long-term treatment of primary biliary cirrhosis. The udca-pbc study group","volume":"330","author":"Poupon","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1124\/jpet.105.084905","article-title":"A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis","volume":"314","author":"Fiorucci","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1053\/j.gastro.2014.12.005","article-title":"Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid","volume":"148","author":"Hirschfield","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1365-2036.2010.04512.x","article-title":"Pilot study: Fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid","volume":"33","author":"Levy","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1002\/cpt.1930","article-title":"Fenofibrate improves liver function and reduces the toxicity of the bile acid pool in patients with primary biliary cholangitis and primary sclerosing cholangitis who are partial responders to ursodiol","volume":"108","author":"Ghonem","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/apt.15049","article-title":"Letter: Reduction in projected mortality or need for liver transplantation associated with bezafibrate add-on in primary biliary cholangitis with incomplete udca response","volume":"49","author":"Corpechot","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_202","first-page":"734","article-title":"Fibrates for itch (fitch) in fibrosing cholangiopathies: A double-blind, randomized, placebo-controlled trial","volume":"160","author":"Bolier","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_203","first-page":"521","article-title":"Fibrates improve liver tests in primary sclerosing cholangitis with incomplete biochemical response to ursodeoxycholic acid: Update of a pilote study: 335","volume":"60","author":"Lemoinne","year":"2014","journal-title":"Hepatology"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1016\/S0168-8278(18)30429-X","article-title":"Treatment efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor delta agonist, in primary biliary cholangitis patients: 12-and 26-week analysis from an ongoing international, randomized, dose raging phase 2 study","volume":"68","author":"Hirschfield","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Schattenberg, J.M., Pares, A., Kowdley, K.V., Heneghan, M.A., Caldwell, S., Pratt, D., Bonder, A., Hirschfield, G.M., Levy, C., and Vierling, J. (2021). A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to udca. J. Hepatol.","DOI":"10.1016\/j.jhep.2021.01.013"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/hep.22906","article-title":"Primary biliary cirrhosis","volume":"50","author":"Lindor","year":"2009","journal-title":"Hepatology"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1002\/hep.30509","article-title":"The nonsteroidal farnesoid x receptor agonist cilofexor (gs-9674) improves markers of cholestasis and liver injury in patients with primary sclerosing cholangitis","volume":"70","author":"Trauner","year":"2019","journal-title":"Hepatology"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1111\/liv.13880","article-title":"Novel and emerging therapies for cholestatic liver diseases","volume":"38","author":"Goldstein","year":"2018","journal-title":"Liver Int."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/liv.13744","article-title":"Time for the dawn of multimodal therapies and the dusk for mono-therapeutic trials for cholestatic liver diseases?","volume":"38","author":"Wagner","year":"2018","journal-title":"Liver Int."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/hep.30099","article-title":"Rituximab is ineffective for treatment of fatigue in primary biliary cholangitis: A phase 2 randomized controlled trial","volume":"70","author":"Khanna","year":"2019","journal-title":"Hepatology"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/hep.30237","article-title":"Simtuzumab for primary sclerosing cholangitis: Phase 2 study results with insights on the natural history of the disease","volume":"69","author":"Muir","year":"2019","journal-title":"Hepatology"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1080\/00365521.2020.1787501","article-title":"Open-label prospective therapeutic clinical trials: Oral vancomycin in children and adults with primary sclerosing cholangitis","volume":"55","author":"Ali","year":"2020","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/apt.12232","article-title":"Randomised clinical trial: Vancomycin or metronidazole in patients with primary sclerosing cholangitis\u2014A pilot study","volume":"37","author":"Tabibian","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1097\/MJT.0000000000000102","article-title":"Prospective clinical trial of rifaximin therapy for patients with primary sclerosing cholangitis","volume":"24","author":"Tabibian","year":"2017","journal-title":"Am. J. Ther."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1097\/MCG.0000000000000591","article-title":"Combination therapy of all-trans retinoic acid with ursodeoxycholic acid in patients with primary sclerosing cholangitis: A human pilot study","volume":"51","author":"Assis","year":"2017","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/13543784.2021.1857364","article-title":"Investigational drugs in early phase development for primary biliary cholangitis","volume":"30","author":"Gochanour","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jhep.2018.10.035","article-title":"Effect of ngm282, an fgf19 analogue, in primary sclerosing cholangitis: A multicenter, randomized, double-blind, place-bo-controlled phase ii trial","volume":"70","author":"Hirschfield","year":"2019","journal-title":"J. Hepatol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:57:12Z","timestamp":1760162232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":217,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["cells10051107"],"URL":"https:\/\/doi.org\/10.3390\/cells10051107","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]}}}