{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T02:31:53Z","timestamp":1776220313655,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T00:00:00Z","timestamp":1520553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["15K08341"],"award-info":[{"award-number":["15K08341"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Cellular senescence plays a role in tumour suppression and in the pathogenesis of various non\u2010neoplastic diseases, including primary biliary cholangitis and other adult cholangiopathies. Less is known about the role of cellular senescence in cholangiopathies in children. With that in mind, we examined the expression of senescence\u2010associated cell cycle regulators in biliary atresia, the most common form of paediatric obliterative cholangiopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The expression of senescence\u2010associated cell cycle regulators (p16<jats:sup>Ink4a<\/jats:sup> and p21<jats:styled-content style=\"fixed-case\"><jats:sup>WAF<\/jats:sup><\/jats:styled-content><jats:sup>1\/Cip1<\/jats:sup>) and a ductular reaction related marker (neural cell adhesion molecule: <jats:styled-content style=\"fixed-case\">NCAM<\/jats:styled-content>) was examined in bile ducts and bile ductules in liver samples taken from the patients with biliary atresia [<jats:italic>n<\/jats:italic> = 80; including 23 samples at the time of the Kasai procedure (<jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content>) and 63 obtained from the explanted liver (<jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content>) (six cases with samples at both surgical stages of disease)] and from appropriate controls (<jats:italic>n<\/jats:italic> = 17). The degree of ductular reaction and cholestasis was significantly more extensive in <jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content> than <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content> (<jats:italic>P<\/jats:italic> &lt; 0.01). The expression of p16<jats:styled-content style=\"fixed-case\"><jats:sup>INK<\/jats:sup><\/jats:styled-content><jats:sup>4a<\/jats:sup> and <jats:styled-content style=\"fixed-case\">NCAM<\/jats:styled-content> was significantly more extensive in bile ducts and bile ductules in ductular reaction in both <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content> compared to controls and in <jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content> compared to <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content> (<jats:italic>P<\/jats:italic> &lt; 0.05). The expression of p21<jats:styled-content style=\"fixed-case\"><jats:sup>WAF<\/jats:sup><\/jats:styled-content><jats:sup>1\/Cip1<\/jats:sup> was significantly more extensive in bile ducts and bile ductules in <jats:styled-content style=\"fixed-case\">KP<\/jats:styled-content> compared to both <jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content> and controls (<jats:italic>P<\/jats:italic> &lt; 0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cellular senescence may play a role in the progression of bile duct loss in biliary atresia in a manner similar to that of adult cholangiopathies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13476","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T06:36:48Z","timestamp":1517553408000},"page":"1164-1171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Increased expression of senescence\u2010associated cell cycle regulators in the progression of biliary atresia: an immunohistochemical study"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-760X","authenticated-orcid":false,"given":"Motoko","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Human Pathology Kanazawa University Graduate School of Medicine Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang\u2010Ying","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Pathology Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao\u2010Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul E","family":"Swanson","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington School of Medicine Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao\u2010Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiin\u2010Haur","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew M","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington School of Medicine Seattle WA USA"},{"name":"Department of Medicine University of Washington School of Medicine Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2015.03.017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.11.027"},{"key":"e_1_2_7_4_1","first-page":"517","volume-title":"Diseases of the bile ducts","author":"Portmann B","year":"2007"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2008.09.013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1996.01430170039006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20547"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.04.032"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.06.005"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20130"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63489-X"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280412"},{"key":"e_1_2_7_13_1","first-page":"439","article-title":"Ductular reaction after submassive necrosis in humans. 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