Polyploidy control in hepatic health and disease

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 under...

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Bibliographic Details
Published inJournal of hepatology Vol. 75; no. 5; pp. 1177 - 1191
Main Authors Sladky, Valentina C., Eichin, Felix, Reiberger, Thomas, Villunger, Andreas
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.11.2021
Elsevier Science Ltd
Subjects
Cardiomyocytes
Centrosomes
Genetic transformation
HCC
Hepatocellular carcinoma
Hepatocyte
Hepatocytes
Humans
inflammatory liver disease
Liver - drug effects
Liver - pathology
Liver - physiopathology
Liver cancer
Liver diseases
Liver Neoplasms - pathology
Megakaryocytes
Molecular modelling
Osteoclasts
p53
p53 Protein
PIDDosome
Ploidy
Polyploidy
Prognosis
Signal transduction
Signal Transduction - drug effects
Signal Transduction - genetics
inflammatory liver disease
PIDDosome
HCC
Polyploidy
Hepatocyte
p53
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Summary: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.
ISSN:0168-8278
1600-0641
DOI:10.1016/j.jhep.2021.06.030