{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:44:47Z","timestamp":1791081887509,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T00:00:00Z","timestamp":1226275200000},"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":[[2009,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Infections of Reoviridae consisting of a double\u2010stranded RNA (dsRNA) genome and the biliary innate immune response to dsRNA are implicated in the aetiopathogenesis of biliary atresia (BA). Epithelial\u2013mesenchymal transition (EMT) has recently been proposed as a mechanism behind the sclerosing cholangitis in BA. We hypothesized that the innate immune response to dsRNA in biliary epithelial cells plays an important role in peribiliary fibrosis via biliary EMT. Experiments using cultured human biliary epithelial cells revealed that stimulation with poly(I : C) (a synthetic analogue of viral dsRNA) increased the expression of basic fibroblast growth factor (bFGF, an EMT\u2010inducer), S100A4 (a mesenchymal marker) and Snail (a transcriptional factor), and decreased that of epithelial markers (biliary\u2010type cytokeratin 19 and E\u2010cadherin) and Bambi (TGF\u2010\u03b21 pseudoreceptor). The expression of TGF\u2010\u03b21 (EMT\u2010inducer) and vimentin (a mesenchymal marker) was not affected by poly(I : C). Both EMT\u2010inducers, bFGF and TGF\u2010\u03b21, evoked a decrease and increase in the expression of the epithelial markers and of vimentin respectively, and the expression of Bambi was down\u2010regulated on stimulation with bFGF. Combined treatment with bFGF and TGF\u2010\u03b21 quickly and completely induced a transformation of morphology as well as change from epithelial to mesenchymal features in cultured biliary epithelial cells. Immunohistochemistry revealed that biliary epithelial cells lining extrahepatic bile ducts and peribiliary glands in BA frequently show a lack of epithelial markers and an aberrant expression of vimentin. Moreover, the biliary epithelium showing sclerosing cholangitis expressed bFGF accompanied by bFGF\u2010positive mononuclear cells. In conclusion, the EMT may contribute to the histogenesis of sclerosing cholangiopathy, and the biliary innate immune response to dsRNA viruses induces biliary epithelial cells to undergo EMT via the production of bFGF and the increased susceptibility to TGF\u2010\u03b21 caused by the down\u2010regulation of Bambi expression. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2488","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T09:18:17Z","timestamp":1226308697000},"page":"654-664","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Epithelial\u2013mesenchymal transition induced by biliary innate immunity contributes to the sclerosing cholangiopathy of biliary 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