Biomolecules & Therapeutics
Polyploidization of Hepatocytes: Insights into the Pathogenesis of Liver Diseases
Ju-Yeon Kim1, Haena Choi1, Hyeon-Ji Kim1,2, Yelin Jee1, Minsoo Noh1,2 and Mi-Ock Lee1,2,3,*
1College of Pharmacy, Seoul National University, Seoul 00826,
2Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 00826,
3Bio-MAX institute, Seoul National University, Seoul 08826, Republic of Korea
Tel: +82-2-880-9331, Fax: +82-2-888-9122
Received: May 19, 2022; Revised: May 27, 2022; Accepted: May 28, 2022; Published online: July 5, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.
Keywords: Polyploidization, Hepatocytes, NAFLD, HCC

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