Polyploidy control in hepatic health and disease.

Autor: Sladky VC; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Eichin F; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Reiberger T; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), 1090 Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria., Villunger A; Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), 1090 Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Electronic address: andreas.villunger@i-med.ac.at.
Jazyk: angličtina
Zdroj: Journal of hepatology [J Hepatol] 2021 Nov; Vol. 75 (5), pp. 1177-1191. Date of Electronic Publication: 2021 Jul 03.
DOI: 10.1016/j.jhep.2021.06.030
Abstrakt: A balanced increase in DNA content (ploidy) is observed in some human cell types, including bone-resorbing osteoclasts, platelet-producing megakaryocytes, cardiomyocytes or hepatocytes. The impact of increased hepatocyte ploidy on normal physiology and diverse liver pathologies is still poorly understood. Recent findings suggest swift genetic adaptation to hepatotoxic stress and the protection from malignant transformation as beneficial effects. Herein, we discuss the molecular mechanisms regulating hepatocyte polyploidisation and its implication for different liver diseases and hepatocellular carcinoma. We report on centrosomes' role in limiting polyploidy by activating the p53 signalling network (via the PIDDosome multiprotein complex) and we discuss the role of this pathway in liver disease. Increased hepatocyte ploidy is a hallmark of hepatic inflammation and may play a protective role against liver cancer. Our evolving understanding of hepatocyte ploidy is discussed from the perspective of its potential clinical application for risk stratification, prognosis, and novel therapeutic strategies in liver disease and hepatocellular carcinoma.
Competing Interests: Conflict of Interest TR received grant support from Abbvie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Abbvie, Boehringer-Ingelheim, Gilead and Roche. All other authors declare no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details.
(Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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