Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Polyploidization of Hepatocytes: Insights into the Pathogenesis of Liver Diseases

  • Kim, Ju-Yeon (College of Pharmacy, Seoul National University) ;
  • Choi, Haena (College of Pharmacy, Seoul National University) ;
  • Kim, Hyeon-Ji (College of Pharmacy, Seoul National University) ;
  • Jee, Yelin (College of Pharmacy, Seoul National University) ;
  • Noh, Minsoo (College of Pharmacy, Seoul National University) ;
  • Lee, Mi-Ock (College of Pharmacy, Seoul National University)
  • Received : 2022.05.19
  • Accepted : 2022.05.28
  • Published : 2022.09.01
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Abstract

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

Acknowledgement

This study was supported by grants from the National Research Foundation of Korea (2022R1A2C2006318 and 2018R1A5A2024425), and Korea Mouse Phenotyping Project (2014M3A9D5A01073556).

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