{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T23:48:18Z","timestamp":1768434498232,"version":"3.49.0"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T00:00:00Z","timestamp":1317081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Given autophagy is involved in the pathogenesis in primary biliary cirrhosis (<jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>), we examined an involvement of p62 sequestosome\u20101 (p62), a specific cargo for autophagy, in the process of autophagy and cellular senescence in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined immunohistochemically the expression of p62 in livers taken from patients with <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> (n\u00a0=\u00a046) and control livers (n\u00a0=\u00a078) and its colocalization with microtubule\u2010associated proteins\u2010light chain 3\u03b2 (<jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3), lysosome\u2010associated membrane protein\u20101 (<jats:styled-content style=\"fixed-case\">LAMP<\/jats:styled-content>\u20101) and senescent markers (p16<jats:styled-content style=\"fixed-case\"><jats:sup>INK<\/jats:sup><\/jats:styled-content><jats:sup>4a<\/jats:sup> and p21<jats:styled-content style=\"fixed-case\"><jats:sup>WAF<\/jats:sup><\/jats:styled-content><jats:sup>1\/Cip1<\/jats:sup>). We examined the expression of p62 and <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3 in cultured biliary epithelial cells (<jats:styled-content style=\"fixed-case\">BEC<\/jats:styled-content>s) treated with various stress. The effect of p62 knockdown with <jats:italic>si<\/jats:italic><jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> on stress\u2010induced autophagy and cellular senescence was also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of p62 was specifically seen in cytoplasmic aggregates in <jats:styled-content style=\"fixed-case\">BEC<\/jats:styled-content>s in the inflamed and damaged small bile ducts (<jats:styled-content style=\"fixed-case\">SBD<\/jats:styled-content>s) in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>, when compared with non\u2010inflamed ones in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> and in control livers (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). The co\u2010expression of p62 with <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">LAMP<\/jats:styled-content>\u20101 and senescent markers was seen in the inflamed <jats:styled-content style=\"fixed-case\">SBD<\/jats:styled-content>s in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>, but the intracytoplasmic localization was different. The expression of p62 and <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3 was significantly upregulated in <jats:styled-content style=\"fixed-case\">BEC<\/jats:styled-content>s treated with various stress (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and pretreatment with bafilomycin A1 enhanced the accumulation of p62\u2010positive aggregates in <jats:styled-content style=\"fixed-case\">BEC<\/jats:styled-content>s with serum deprivation. The knockdown of p62 decreased stress\u2010induced autophagy and cellular senescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The aggregation of p62 is specifically increased in the damage bile ducts in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> and may reflect dysfunctional autophagy, followed by cellular senescence in the pathogenesis of bile duct lesions in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2011.02656.x","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T05:37:41Z","timestamp":1317188261000},"page":"487-499","source":"Crossref","is-referenced-by-count":51,"title":["A possible involvement of p62\/sequestosome\u20101 in the process of biliary epithelial autophagy and senescence in primary biliary cirrhosis"],"prefix":"10.1111","volume":"32","author":[{"given":"Motoko","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Human Pathology Kanazawa University Graduate School of Medicine Kanazawa 920\u20108640 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Miyakoshi","sequence":"additional","affiliation":[{"name":"Department of Human Pathology Kanazawa University Graduate School of Medicine Kanazawa 920\u20108640 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunori","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Human Pathology Kanazawa University Graduate School of Medicine Kanazawa 920\u20108640 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuni","family":"Nakanuma","sequence":"additional","affiliation":[{"name":"Department of Human Pathology Kanazawa University Graduate School of Medicine Kanazawa 920\u20108640 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,9,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06639"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/35056522"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.519709"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1795309"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.018"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22146"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00175.2003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23645"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07976"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/ncb2021","article-title":"The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1","volume":"12","author":"Komoatsu M","year":"2010","journal-title":"Nat Cell Biol"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.56"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.048"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05268"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.038"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.039"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.032"},{"key":"e_1_2_7_18_1","first-page":"517","volume-title":"Pathology of the Liver","author":"Portmann B","year":"2007"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043898"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22906"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(79)90396-2"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.22.8654"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214698"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4213"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1729"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.051237"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22348"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2008.03.005"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.13.8892"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802182200"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507002"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702824200"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200107200-00009"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.32674"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64369-6"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.035"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200711108"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001603"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840100209"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20130"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840190629"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00618866"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0676.1998.tb00133.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.6.1889"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.3.1025-1040.2005"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.27544"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.028"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9363"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.3.2109"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0801"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100050"},{"key":"e_1_2_7_52_1","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/S0016-5085(19)32737-4","article-title":"Ultrastructural aspects of primary biliary cirrhosis and other types of cholestatic liver disease","volume":"67","author":"Chedid A","year":"1974","journal-title":"Gastroenterology"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0910-842"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1205407"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1478-3231.2011.02656.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1478-3231.2011.02656.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T07:40:06Z","timestamp":1700552406000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1478-3231.2011.02656.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,27]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1111\/j.1478-3231.2011.02656.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1478-3231.2011.02656.x","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,27]]}}}