Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are human primary cholangiopathies characterized by the damage of mature cholangiocytes and by the appearance of ductular reaction (DR) as the results of hepatic progenitor cell activation. This study evaluated the differences in progenitor cell niche activation between these two cholangiopathies. Liver tissue was obtained from healthy liver donors (n = 5) and from patients with PSC (n = 20) or PBC (n = 20). DR, progenitor cell phenotype, and signaling pathways were investigated by IHC analysis and immunofluorescence. Our results indicated that DR was more extended, appeared earlier, and had a higher proliferation index in PBC compared with PSC. In PBC, DR was strongly correlated with clinical prognostic scores. A higher percentage of transcription factor SOX9+ and keratin 19+ cells but fewer features of hepatocyte fate characterized progenitor cell activation in PBC versus PSC. Lower levels of laminin and neurogenic locus notch homolog protein 1 pathway components but higher expression of wingless-type mouse mammary tumor virus integration site family (WNT) pathway components characterize progenitor cell niche in PSC compared with PBC. In conclusion, progenitor cell activation differs between PSC and PBC and is characterized by a divergent fate commitment and different signaling pathway predominance. In PBC, DR represents a relevant histologic prognostic marker.

Hepatic Stem/Progenitor Cell Activation Differs between Primary Sclerosing and Primary Biliary Cholangitis / Carpino, Guido; Cardinale, Vincenzo; Folseraas, Trine; Overi, Diletta; Floreani, Annarosa; Franchitto, Antonio; Onori, Paolo; Cazzagon, Nora; Berloco, Pasquale Bartolomeo; Karlsen, Tom Hemming; Alvaro, Domenico; Gaudio, Eugenio. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - (2018). [10.1016/j.ajpath.2017.11.010]

Hepatic Stem/Progenitor Cell Activation Differs between Primary Sclerosing and Primary Biliary Cholangitis

Cardinale, Vincenzo;Overi, Diletta;Franchitto, Antonio;Onori, Paolo;Berloco, Pasquale Bartolomeo;Alvaro, Domenico;Gaudio, Eugenio
2018

Abstract

Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are human primary cholangiopathies characterized by the damage of mature cholangiocytes and by the appearance of ductular reaction (DR) as the results of hepatic progenitor cell activation. This study evaluated the differences in progenitor cell niche activation between these two cholangiopathies. Liver tissue was obtained from healthy liver donors (n = 5) and from patients with PSC (n = 20) or PBC (n = 20). DR, progenitor cell phenotype, and signaling pathways were investigated by IHC analysis and immunofluorescence. Our results indicated that DR was more extended, appeared earlier, and had a higher proliferation index in PBC compared with PSC. In PBC, DR was strongly correlated with clinical prognostic scores. A higher percentage of transcription factor SOX9+ and keratin 19+ cells but fewer features of hepatocyte fate characterized progenitor cell activation in PBC versus PSC. Lower levels of laminin and neurogenic locus notch homolog protein 1 pathway components but higher expression of wingless-type mouse mammary tumor virus integration site family (WNT) pathway components characterize progenitor cell niche in PSC compared with PBC. In conclusion, progenitor cell activation differs between PSC and PBC and is characterized by a divergent fate commitment and different signaling pathway predominance. In PBC, DR represents a relevant histologic prognostic marker.
2018
01 Pubblicazione su rivista::01a Articolo in rivista
Hepatic Stem/Progenitor Cell Activation Differs between Primary Sclerosing and Primary Biliary Cholangitis / Carpino, Guido; Cardinale, Vincenzo; Folseraas, Trine; Overi, Diletta; Floreani, Annarosa; Franchitto, Antonio; Onori, Paolo; Cazzagon, Nora; Berloco, Pasquale Bartolomeo; Karlsen, Tom Hemming; Alvaro, Domenico; Gaudio, Eugenio. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - (2018). [10.1016/j.ajpath.2017.11.010]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1058962
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