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In this study, we analysed a signalling pathway that comprises the transcription factor FoxO3a and its downstream target Bim, a Bcl\u20102 interacting mediator of apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials &amp; Methods<\/jats:title><jats:p>The tissues examined included livers explanted from patients with cirrhotic PBC, primary sclerosing cholangitis (PSC), alcoholic liver disease (ALD) and liver biopsies from patients with non\u2010cirrhotic PBC. Large margin resections of hepatocellular carcinoma were used as controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of FoxO3a and Bim <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> was significantly enhanced in both non\u2010cirrhotic and end\u2010stage PBC (2.2\u2010fold and 4.3\u2010fold increases, respectively), but not in the other disorders. Similarly, FOXO3a protein level was increased in end\u2010stage PBC (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 vs. control). A significant increase in Bim <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> in non\u2010cirrhotic and cirrhotic PBC was observed (2.2\u2010fold and 8.2\u2010fold respectively). In addition, the most pro\u2010apoptotic isoform of Bim dominated in livers of PBC patients (2.5\u2010 fold increase vs. control; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Enhanced FoxO3a and Bim expression was associated with a substantial activation of caspase\u20103 in PBC (2\u2010fold increase vs. controls; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), whereas it was decreased in both ALD and PSC (46% and 67% reductions respectively).<\/jats:p><jats:p>The relationship between FoxO3a and Bim was further investigated in the livers of FoxO\u2010deficient mice. The somatic deletion of FoxO3a caused a significant decrease in Bim, but not caspase\u20103 protein expression confirming the crucial role of FoxO3a in induction of Bim gene transcription.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results imply that the FoxO3\/Bim signalling pathway can be of importance in the livers of patients with <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12030","type":"journal-article","created":{"date-parts":[[2012,11,2]],"date-time":"2012-11-02T07:41:07Z","timestamp":1351842067000},"page":"231-238","source":"Crossref","is-referenced-by-count":23,"title":["Activation of FoxO3a\/Bim axis in patients with Primary Biliary Cirrhosis"],"prefix":"10.1111","volume":"33","author":[{"given":"Justyna","family":"Kopycinska","sequence":"first","affiliation":[{"name":"Medical Biology Laboratory Pomeranian Medical University Szczecin 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