{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:25:15Z","timestamp":1790976315879,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,1,31]],"date-time":"2005-01-31T00:00:00Z","timestamp":1107129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pathogenesis of progressive bile duct loss in primary biliary cirrhosis remains unclear. In this study, the involvement of cellular senescence of biliary epithelial cells was examined in liver tissue samples from patients with primary biliary cirrhosis (<jats:italic>n<\/jats:italic> = 33), and compared with control diseased and normal livers (<jats:italic>n<\/jats:italic> = 83). In addition, cellular senescence was induced by oxidative stress in cultured mouse biliary epithelial cells. Biliary epithelial cells in small bile ducts in primary biliary cirrhosis, especially those in patients presenting with chronic non\u2010suppurative cholangitis, frequently expressed senescence\u2010associated \u03b2\u2010galactosidase, and senescence\u2010associated p16<jats:sup>INK4<\/jats:sup> and p21<jats:sup>WAF1\/CIP<\/jats:sup>. In contrast, senescence\u2010associated markers were rarely expressed in small bile ducts in control livers. The infiltration of myeloperoxidase\u2010positive inflammatory cells into biliary epithelial cell layers was closely associated with the cellular senescence of biliary epithelial cells in early\u2010stage PBC. Cellular senescence of cultured mouse biliary epithelial cells was induced by treatment with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> via the p38MAPK\u2010dependent pathway and nitric oxide\u2010augmented H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced cellular senescence. Oxidative stress\u2010 and nitric oxide\u2010mediated cellular senescence may be involved in bile duct lesions, which are followed by progressive bile duct loss in primary biliary cirrhosis. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. 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