{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:28:30Z","timestamp":1790497710324,"version":"4.1.0"},"reference-count":39,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18590325"],"award-info":[{"award-number":["18590325"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","journal-of-hepatology.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Hepatology"],"published-print":{"date-parts":[[2010,8]]},"DOI":"10.1016\/j.jhep.2010.03.008","type":"journal-article","created":{"date-parts":[[2010,5,6]],"date-time":"2010-05-06T04:31:34Z","timestamp":1273120294000},"page":"318-325","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":102,"title":["Modulation of the microenvironment by senescent biliary epithelial cells may be involved in the pathogenesis of primary biliary cirrhosis"],"prefix":"10.1016","volume":"53","author":[{"given":"Motoko","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Miyakoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuni","family":"Nakanuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhep.2010.03.008_bib1","first-page":"G1260","article-title":"Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events","volume":"276","author":"Sigal","year":"1999","journal-title":"Am J Physiol"},{"key":"10.1016\/j.jhep.2010.03.008_bib2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0074-7696(08)60100-X","article-title":"Cell polyploidy: its relation to tissue growth and function","volume":"50","author":"Brodsky","year":"1977","journal-title":"Int Rev Cytol"},{"key":"10.1016\/j.jhep.2010.03.008_bib3","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies senescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jhep.2010.03.008_bib4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.cell.2007.07.003","article-title":"Cellular senescence in cancer and aging","volume":"130","author":"Collado","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.jhep.2010.03.008_bib5","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.cell.2008.03.038","article-title":"Chemokine signaling via the CXCR2 receptor reinforces senescence","volume":"133","author":"Acosta","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.jhep.2010.03.008_bib6","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cell.2008.03.039","article-title":"Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network","volume":"133","author":"Kuilman","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.jhep.2010.03.008_bib7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.cell.2007.12.032","article-title":"Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7","volume":"132","author":"Wajapeyee","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.jhep.2010.03.008_bib8","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0960-9822(99)80420-5","article-title":"Microarray analysis of replicative senescence","volume":"9","author":"Shelton","year":"1999","journal-title":"Curr Biol"},{"key":"10.1016\/j.jhep.2010.03.008_bib9","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1371\/journal.pbio.0060301","article-title":"Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor","volume":"6","author":"Coppe","year":"2008","journal-title":"PLoS Biol"},{"key":"10.1016\/j.jhep.2010.03.008_bib10","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1053\/j.gastro.2006.07.023","article-title":"Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver","volume":"132","author":"Alvaro","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2010.03.008_bib11","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/hep.22102","article-title":"Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells","volume":"47","author":"Shimoda","year":"2008","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib12","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH725>3.0.CO;2-P","article-title":"Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: implications for pathogenesis","volume":"193","author":"Tsuneyama","year":"2001","journal-title":"J Pathol"},{"key":"10.1016\/j.jhep.2010.03.008_bib13","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/hep.20582","article-title":"Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts","volume":"41","author":"Isse","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib14","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.4049\/jimmunol.138.10.3525","article-title":"Identification and specificity of a cDNA encoding the 70kDa mitochondrial antigen recognized in primary biliary cirrhosis","volume":"138","author":"Gershwin","year":"1987","journal-title":"J Immunol"},{"key":"10.1016\/j.jhep.2010.03.008_bib15","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1056\/NEJM199611213352107","article-title":"Primary biliary cirrhosis","volume":"335","author":"Kaplan","year":"1996","journal-title":"New Engl J Med"},{"key":"10.1016\/j.jhep.2010.03.008_bib16","series-title":"Pathology of the liver","first-page":"435","article-title":"Diseases of the bile ducts","author":"Portmann","year":"2001"},{"key":"10.1016\/j.jhep.2010.03.008_bib17","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/0016-5085(79)90396-2","article-title":"Histometric and serial section observations of the intrahepatic bile ducts in primary biliary cirrhosis","volume":"76","author":"Nakanuma","year":"1979","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2010.03.008_bib18","doi-asserted-by":"crossref","first-page":"8654","DOI":"10.1073\/pnas.85.22.8654","article-title":"Identification and analysis of the major M2 autoantigens in primary biliary cirrhosis","volume":"85","author":"Fussey","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.jhep.2010.03.008_bib19","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 Invest"},{"key":"10.1016\/j.jhep.2010.03.008_bib20","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1172\/JCI4213","article-title":"Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis","volume":"102","author":"Shimoda","year":"1998","journal-title":"J Clin Invest"},{"key":"10.1016\/j.jhep.2010.03.008_bib21","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/hep.22348","article-title":"Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence","volume":"48","author":"Sasaki","year":"2008","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/path.1729","article-title":"Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss","volume":"205","author":"Sasaki","year":"2005","journal-title":"J Pathol"},{"key":"10.1016\/j.jhep.2010.03.008_bib23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaut.2008.03.005","article-title":"Activation of ATM signaling pathway is involved in oxidative stress-induced expression of mito-inhibitory p21(WAF1\/Cip1) in chronic non-suppurative destructive cholangitis in primary biliary cirrhosis: An immunohistochemical study","volume":"31","author":"Sasaki","year":"2008","journal-title":"J Autoimmun"},{"key":"10.1016\/j.jhep.2010.03.008_bib24","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2353\/ajpath.2006.051237","article-title":"Decreased expression of Bmi-1 is closely associated with cellular senescence in small bile ducts in primary biliary cirrhosis","volume":"169","author":"Sasaki","year":"2006","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jhep.2010.03.008_bib25","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":"10.1016\/j.jhep.2010.03.008_bib26","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cell.2008.06.049","article-title":"Senescence of activated stellate cells limits liver fibrosis","volume":"134","author":"Krizhanovsky","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.jhep.2010.03.008_bib27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1053\/hupa.2001.22747","article-title":"Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas","volume":"32","author":"Paradis","year":"2001","journal-title":"Hum Pathol"},{"key":"10.1016\/j.jhep.2010.03.008_bib28","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1096\/fj.01-0977com","article-title":"Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis","volume":"16","author":"Wiemann","year":"2002","journal-title":"Faseb J"},{"key":"10.1016\/j.jhep.2010.03.008_bib29","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/hep.21552","article-title":"Telomere shortening and inactivation of cell cycle checkpoints characterize human hepatocarcinogenesis","volume":"45","author":"Plentz","year":"2007","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib30","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/hep.20847","article-title":"Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma","volume":"42","author":"Plentz","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib31","first-page":"89","article-title":"Increased expression of interleukin-6 and tumor necrosis factor-alpha in pathologic biliary epithelial cells: in situ and culture study","volume":"78","author":"Yasoshima","year":"1998","journal-title":"Lab Invest"},{"key":"10.1016\/j.jhep.2010.03.008_bib32","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/S0002-9440(10)64423-9","article-title":"Lipopolysaccharide induces overexpression of MUC2 and MUC5AC in cultured biliary epithelial cells: possible key phenomenon of hepatolithiasis","volume":"161","author":"Zen","year":"2002","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jhep.2010.03.008_bib33","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/hep.1840100209","article-title":"Expression of blood-group-related antigens in the intrahepatic biliary tree and hepatocytes in normal livers and various hepatobiliary diseases","volume":"10","author":"Nakanuma","year":"1989","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1055\/s-2008-1040417","article-title":"Small-duct primary sclerosing cholangitis","volume":"11","author":"Ludwig","year":"1991","journal-title":"Semin Liver Dis"},{"key":"10.1016\/j.jhep.2010.03.008_bib35","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/hep.1840190629","article-title":"Classification of chronic hepatitis: diagnosis, grading and staging","volume":"19","author":"Desmet","year":"1994","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib36","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1053\/jhep.2001.25086","article-title":"Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis","volume":"33","author":"Sakisaka","year":"2001","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2010.03.008_bib37","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nature05529","article-title":"Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas","volume":"445","author":"Xue","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.jhep.2010.03.008_bib38","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/S0955-0674(00)00278-7","article-title":"Putting the stress on senescence","volume":"13","author":"Serrano","year":"2001","journal-title":"Curr Opin Cell Biol"},{"key":"10.1016\/j.jhep.2010.03.008_bib39","series-title":"Biliary and pancreatic ductal epithelia","first-page":"127","article-title":"Immunopathology of the human biliary tree","author":"Demetris","year":"1997"}],"container-title":["Journal of Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827810003247?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827810003247?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:31:43Z","timestamp":1759174303000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168827810003247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["S0168827810003247"],"URL":"https:\/\/doi.org\/10.1016\/j.jhep.2010.03.008","relation":{},"ISSN":["0168-8278"],"issn-type":[{"value":"0168-8278","type":"print"}],"subject":[],"published":{"date-parts":[[2010,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Modulation of the microenvironment by senescent biliary epithelial cells may be involved in the pathogenesis of primary biliary cirrhosis","name":"articletitle","label":"Article Title"},{"value":"Journal of Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhep.2010.03.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2010 European Association for the Study of the Liver. Published by Elsevier Ireland Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}