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Hepatic stem/progenitor cell activation differs between primary sclerosing and primary biliary cholangitis.

著者 Carpino G , Cardinale V , Folseraas T , Overi D , Floreani A , Franchitto A , Onori P , Cazzagon N , Berloco PB , Karlsen TH , Alvaro D , Gaudio E
Am J Pathol.2017 Dec 14 ; ():.
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Primary sclerosing cholangitis and primary biliary cholangitis are human primary cholangiopathies; these diseases are characterized by the damage of mature cholangiocytes and by the appearance of ductular reaction as the results of hepatic progenitor cell activation. The aims of this study were to evaluate differences in progenitor cell niche activation between these two human cholangiopathies. Human liver tissue was obtained from normal liver donors (n=5), primary sclerosing (n=20), and primary biliary cholangitis (n=20). Ductular reaction, progenitor cell phenotype, and signaling pathways were investigated by immunohistochemistry and immunofluorescence. Our results indicated that ductular reaction is more extended, appears earlier, and has a higher proliferation index in primary biliary cholangitis compared to primary sclerosing cholangitis. In primary biliary cholangitis, ductular reaction strongly correlates with clinical prognostic scores. A higher percentage of Sox9+ and Keratin-19+ cells but lower features of hepatocyte fate characterize progenitor cell activation in primary biliary cholangitis versus primary sclerosing cholangitis. Lower levels of laminin and NOTCH1 but higher expression of WNT pathway components characterize progenitor cell niche in primary sclerosing cholangitis compared to primary biliary cholangitis. In conclusion, progenitor cell activation differs between primary sclerosing cholangitis and primary biliary cholangitis and is characterized by a divergent fate commitment and different signaling pathway predominance. In primary biliary cholangitis, ductular reaction represents a relevant histologic prognostic marker.
PMID: 29248458 [PubMed - as supplied by publisher]
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