{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:18:34Z","timestamp":1790252314872,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1614,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Chronic diseases of the biliary system are common and may cause fibrosis and eventually progression to liver cirrhosis. The aim was to define a new mouse model of a cholangiopathy leading to liver fibrosis in<\/jats:bold>\n                                 <jats:bold>\n                                    fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>mice. Liver pathology of<\/jats:bold>\n                                 <jats:bold>\n                                    fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>mice was analyzed in detail by histology and flow cytometry. Transcript levels of fibrosis-related genes and matrix metalloproteinase (MMP) activities were quantified and immunohistochemical analysis additionally applied. The role of the immune system in this model was analyzed by crossing<\/jats:bold>\n                                 <jats:bold>\n                                    fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>mice with<\/jats:bold>\n                                 <jats:bold>\n                                    rag2\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    -\/- mice. Furthermore, expression of Fra-1 in corresponding human liver diseases was investigated on transcription level and histologically.<\/jats:bold>\n                                 <jats:bold>\n                                    Fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>mice spontaneously develop biliary fibrosis preceded by ductular proliferation and infiltration of inflammatory cells.<\/jats:bold>\n                                 <jats:bold>\n                                    Fra-1\n                                 <\/jats:bold>\n                                 <jats:bold>protein is present in cholangiocytes and inflammatory cells within the liver. These findings were replicated in human biopsies of patients with advanced liver fibrosis. The inflammatory infiltrate showed a strong increase in activated T cells and decreased natural killer (NK), natural killer T cells (NKT), and B cells in<\/jats:bold>\n                                 <jats:bold>\n                                    fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>mice as compared to wildtype mice. Moreover,<\/jats:bold>\n                                 <jats:bold>\n                                    fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>mice develop biliary fibrosis with a time-dependent increase in hepatic collagen content and increase in relative messenger RNA (mRNA) expression of profibrotic genes. Attenuation but not complete prevention of collagen accumulation in liver was observed in the<\/jats:bold>\n                                 <jats:bold>\n                                    fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>\u00d7<\/jats:bold>\n                                 <jats:bold>\n                                    rag2-\/-\n                                    \n                                 <\/jats:bold>\n                                 <jats:bold>mice. However, transplantation of<\/jats:bold>\n                                 <jats:bold>\n                                    fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>bone marrow cells into wildtype mice could not induce disease.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    Fra-1tg\n                                 <\/jats:bold>\n                                 <jats:bold>mice spontaneously develop a progressive biliary disease. These mice are an attractive model for the investigation of cholangiopathies and their interaction with the immune system. (HEPATOLOGY 2011;)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.24175","type":"journal-article","created":{"date-parts":[[2011,1,10]],"date-time":"2011-01-10T18:07:39Z","timestamp":1294682859000},"page":"1287-1297","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":28,"title":["Transcription factor Fra-1 induces cholangitis and liver 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