{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:59:06Z","timestamp":1791831546021,"version":"4.3.4"},"reference-count":51,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1565\/19"],"award-info":[{"award-number":["1565\/19"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2024,6]]},"DOI":"10.1016\/j.ajpath.2024.01.023","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T16:13:52Z","timestamp":1710519232000},"page":"941-957","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sortilin in Biliary Epithelial Cells Promotes Ductular Reaction and Fibrosis during Cholestatic Injury"],"prefix":"10.1016","volume":"194","author":[{"given":"Einav","family":"Hubel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal","family":"Fishman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ortal","family":"Schaffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Erez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bander Abu","family":"Shrkihe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Shteingard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren","family":"Shibolet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Varol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-664X","authenticated-orcid":false,"given":"Isabel","family":"Zvibel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2024.01.023_bib1","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":"Penz-\u00d6sterreicher","year":"2011","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib2","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1053\/j.gastro.2010.09.004","article-title":"Pathogenesis of cholestatic liver disease and therapeutic approaches","volume":"139","author":"Hirschfield","year":"2010","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib3","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.bpg.2011.10.009","article-title":"Pathogenesis of primary sclerosing cholangitis","volume":"25","author":"Pollheimer","year":"2011","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib4","doi-asserted-by":"crossref","first-page":"G1077","DOI":"10.1152\/ajpgi.00227.2012","article-title":"Advances in BEC immunobiology","volume":"303","author":"Syal","year":"2012","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/B978-0-12-416022-4.00010-X","article-title":"The origin, biology, and therapeutic potential of facultative adult hepatic progenitor cells","volume":"107","author":"Shin","year":"2014","journal-title":"Curr Top Dev Biol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib6","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nrn2516","article-title":"VPS10P-domain receptors - regulators of neuronal viability and function","volume":"9","author":"Willnow","year":"2008","journal-title":"Nat Rev Neurosci"},{"key":"10.1016\/j.ajpath.2024.01.023_bib7","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.immuni.2012.07.012","article-title":"The sorting receptor Sortilin exhibits a dual function in exocytic trafficking of interferon-\u03b3 and granzyme A in T cells","volume":"37","author":"Herda","year":"2012","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2024.01.023_bib8","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1128\/MCB.00274-10","article-title":"Sortilin facilitates signaling of ciliary neurotrophic factor and related helical type 1 cytokines targeting the gp130\/leukemia inhibitory factor receptor beta heterodimer","volume":"30","author":"Larsen","year":"2010","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib9","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/hep.510280514","article-title":"Interleukin-6, hepatocyte growth factor, and their receptors in biliary epithelial cells during a type I ductular reaction in mice: interactions between the periductal inflammatory and stromal cells and the biliary epithelium","volume":"28","author":"Liu","year":"1998","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.scr.2008.01.002","article-title":"Signaling networks in hepatic oval cell activation","volume":"1","author":"Erker","year":"2007","journal-title":"Stem Cell Res"},{"key":"10.1016\/j.ajpath.2024.01.023_bib11","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.jhep.2005.04.020","article-title":"Expression of oncostatin M and its receptors in normal and cirrhotic human liver","volume":"43","author":"Znoyko","year":"2005","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib12","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ajpath.2016.09.005","article-title":"Sortilin deficiency reduces ductular reaction, hepatocyte apoptosis, and liver fibrosis in cholestatic-induced liver injury","volume":"187","author":"Hubel","year":"2017","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib13","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1038\/nn2000","article-title":"Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury","volume":"10","author":"Jansen","year":"2007","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.ajpath.2024.01.023_sref14","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.stemcr.2017.06.003","article-title":"Adult mouse liver contains two distinct populations of cholangiocytes","volume":"9","author":"Li","year":"2017","journal-title":"Stem Cell Rep"},{"key":"10.1016\/j.ajpath.2024.01.023_sref15","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.3748\/wjg.v12.i22.3512","article-title":"Biliary wound healing, ductular reactions, and IL-6\/gp130 signaling in the development of liver disease","volume":"12","author":"Demetris","year":"2006","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib15","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1034\/j.1600-0676.2000.020002114.x","article-title":"Acute obstructive cholangiopathy in interleukin-6 deficient mice: compensation by leukemia inhibitory factor (LIF) suggests importance of gp-130 signaling in the ductular reaction","volume":"20","author":"Liu","year":"2000","journal-title":"Liver"},{"key":"10.1016\/j.ajpath.2024.01.023_bib16","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/hep.21535","article-title":"Opposing roles of gp130-mediated STAT-3 and ERK-1\/2 signaling in liver progenitor cell migration and proliferation","volume":"45","author":"Yeoh GC","year":"2007","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib17","first-page":"15","article-title":"Expression of leukemia inhibitory factor and its receptor during liver regeneration in the adult rat","volume":"75","author":"Omori","year":"1996","journal-title":"Lab Invest"},{"key":"10.1016\/j.ajpath.2024.01.023_bib19","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41577-018-0066-7","article-title":"Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer","volume":"18","author":"Jones","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib20","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cytogfr.2015.07.001","article-title":"Leukemia inhibitory factor (LIF)","volume":"26","author":"Nicola","year":"2015","journal-title":"Cytokine Growth Factor Rev"},{"key":"10.1016\/j.ajpath.2024.01.023_bib21","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1053\/j.gastro.2004.06.023","article-title":"Nerve growth factor modulates the proliferative capacity of the intrahepatic biliary epithelium in experimental cholestasis","volume":"127","author":"Gigliozzi","year":"2004","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cell.2021.12.018","article-title":"Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches","volume":"185","author":"Guilliams","year":"2022","journal-title":"Cell"},{"key":"10.1016\/j.ajpath.2024.01.023_bib22","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1136\/gut.2009.186528","article-title":"Curcumin improves sclerosing cholangitis in Mdr2-\/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation","volume":"59","author":"Baghdasaryan","year":"2010","journal-title":"Gut"},{"key":"10.1016\/j.ajpath.2024.01.023_bib23","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/hep.27425","article-title":"Connective tissue growth factor and integrin [alpha]v[beta]6: a new pair of regulators critical for ductular reaction and biliary fibrosis in mice","volume":"61","author":"Pi","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib24","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jhep.2013.02.025","article-title":"Notch signaling regulates tubular morphogenesis during repair from biliary damage in mice","volume":"59","author":"Fiorotto","year":"2013","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib25","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/nm.2940","article-title":"LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker","volume":"18","author":"Chen","year":"2012","journal-title":"Nat Med"},{"key":"10.1016\/j.ajpath.2024.01.023_bib26","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/jcb.20992","article-title":"Scribble associates with two polarity proteins, Lgl2 and Vangl2, via distinct molecular domains","volume":"99","author":"Kallay","year":"2006","journal-title":"J Cell Biochem"},{"key":"10.1016\/j.ajpath.2024.01.023_bib27","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s41467-020-14283-3","article-title":"Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors","volume":"11","author":"Wilson","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2024.01.023_bib28","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1002\/hep.31987","article-title":"Single-cell transcriptomic analysis reveals a hepatic stellate cell-activation roadmap and myofibroblast origin during liver fibrosis in mice","volume":"74","author":"Yang","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib29","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":"10.1016\/j.ajpath.2024.01.023_bib30","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.diff.2016.07.001","article-title":"The characteristics of activated portal fibroblasts\/myofibroblasts in liver fibrosis","volume":"92","author":"Karin","year":"2016","journal-title":"Differentiation"},{"key":"10.1016\/j.ajpath.2024.01.023_bib31","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nm1539","article-title":"Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide","volume":"13","author":"Lang","year":"2007","journal-title":"Nat Med"},{"key":"10.1016\/j.ajpath.2024.01.023_bib32","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/toxsci\/kfx078","article-title":"Sortilin 1 loss-of-function protects against cholestatic liver injury by attenuating hepatic bile acid accumulation in bile duct ligated mice","volume":"161","author":"Li","year":"2018","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.ajpath.2024.01.023_bib33","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":"Planas-Paz","year":"2019","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ajpath.2024.01.023_bib34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3748\/wjg.v17.i2.151","article-title":"Connective tissue growth factor reacts as an IL-6\/STAT3-regulated hepatic negative acute phase protein","volume":"17","author":"Gressner","year":"2011","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/hep.23664","article-title":"Deletion of interleukin-6 in mice with the dominant negative form of transforming growth factor beta receptor II improves colitis but exacerbates autoimmune cholangitis","volume":"52","author":"Zhang","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib36","doi-asserted-by":"crossref","first-page":"11281","DOI":"10.1074\/jbc.M208470200","article-title":"Interleukin-6\/glycoprotein 130-dependent pathways are protective during liver regeneration","volume":"278","author":"Wuestefeld","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2024.01.023_bib37","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.2353\/ajpath.2010.090469","article-title":"Lack of glycoprotein 130\/signal transducer and activator of transcription 3-mediated signaling in hepatocytes enhances chronic liver injury and fibrosis progression in a model of sclerosing cholangitis","volume":"176","author":"Plum","year":"2010","journal-title":"Am J Pathol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib38","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/hep.23322","article-title":"Lack of interleukin-6\/glycoprotein 130\/signal transducers and activators of transcription-3 signaling in hepatocytes predisposes to liver steatosis and injury in mice","volume":"51","author":"Kroy","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib39","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/hep.27268","article-title":"Emerging roles of notch signaling in liver disease","volume":"61","author":"Geisler","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib40","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.cell.2014.03.060","article-title":"Hippo pathway activity influences liver cell fate","volume":"157","author":"Yimlamai","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.ajpath.2024.01.023_bib41","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/hep.25769","article-title":"Yes-associated protein regulates the hepatic response after bile duct ligation","volume":"56","author":"Bai","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib42","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1073\/pnas.1420850112","article-title":"Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules","volume":"112","author":"Yang","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2024.01.023_bib43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ydbio.2012.11.012","article-title":"Scribble is required for normal epithelial cell-cell contacts and lumen morphogenesis in the mammalian lung","volume":"373","author":"Yates","year":"2013","journal-title":"Dev Biol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib44","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.1093\/hmg\/ddq397","article-title":"The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation","volume":"19","author":"Yates","year":"2010","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.ajpath.2024.01.023_bib45","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jhep.2017.11.012","article-title":"Determinants of fibrosis progression and regression in NASH","volume":"68","author":"Schuppan","year":"2018","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib46","article-title":"Understanding the cellular interactome of non-alcoholic fatty liver disease","volume":"4","author":"Wallace","year":"2022","journal-title":"JHEP Rep"},{"key":"10.1016\/j.ajpath.2024.01.023_bib47","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/hep.28274","article-title":"Integrin [alpha]v[beta]6 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis","volume":"63","author":"Peng","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2024.01.023_bib48","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1136\/gutjnl-2013-306373","article-title":"Osteopontin induces ductular reaction contributing to liver fibrosis","volume":"63","author":"Wang","year":"2014","journal-title":"Gut"},{"key":"10.1016\/j.ajpath.2024.01.023_bib49","doi-asserted-by":"crossref","first-page":"G765","DOI":"10.1152\/ajpgi.00308.2005","article-title":"Secretion of MCP-1\/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts","volume":"290","author":"Kruglov","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.ajpath.2024.01.023_bib50","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.atherosclerosis.2015.11.027","article-title":"Protein sorting gone wrong--VPS10P domain receptors in cardiovascular and metabolic diseases","volume":"245","author":"Schmidt","year":"2016","journal-title":"Atherosclerosis"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944024000877?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944024000877?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:54:43Z","timestamp":1748739283000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944024000877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["S0002944024000877"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2024.01.023","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sortilin in Biliary Epithelial Cells Promotes Ductular Reaction and Fibrosis during Cholestatic Injury","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2024.01.023","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 American Society for Investigative Pathology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}