肝细胞多倍化的研究进展

Progress of hepatocyte polyploidization

多倍体肝细胞含有两组或两组以上的DNA染色体组,是哺乳动物成熟肝细胞的典型特征。肝细胞多倍化过程首次发生在出生后的肝脏发育过程中,主要由胰岛素-Akt信号通路调控的细胞质不完全分裂导致。随着年龄的增加,多倍体肝细胞的比例还会继续升高,老年小鼠和人肝脏中多倍体肝细胞比例可高达90%和40%。而当肝脏受到肝脏切除、毒性刺激和代谢过载以及氧化应激等病理损伤时,肝细胞多倍化现象会再次发生。但是,当衰老的多倍体肝细胞在年轻小鼠肝脏中发生增殖时,不仅可产生低倍体肝细胞,还可以逆转其衰老特征。生理和病理过程中多倍体肝细胞的生物学功能备受争议,一般认为与细胞的成熟和终末分化、细胞衰老以及疾病有着重要的关系。本文主要阐述正常生理发育和病理条件下多倍体肝细胞形成过程及潜在的生物学意义,以及多倍体肝细胞逆转对临床肝脏疾病研究的可能提示。

Polyploidy contains more than two sets of chromosomes, which is a characteristic feature of mammalian hepatocytes. Hepatocyte polyploidization first takes place during the course of postnatal development. Most of the polyploidy in hepatocytes has been shown to be a function of failed cytokinesis, regulated by insulin-Akt signaling pathway. Hepatocyte polyploidozation is an age-dependent process. The percentage of polyploidization increases to 90% in mice and 40% in humans in aging liver. Alternatively, hepatocytes modulate its ploidy in response to injury and varieties of stimuli stress, such as toxic stimulation, metabolic overload, or oxidative damage. However, polyploid hepatocytes can generate diploid and tetraploid cells with poloidy reversal when proliferation in the young recipient liver. The biological significance of liver polyploidization during physiologic and pathologic processes remains debatable, but polyploidization is generally considered to be terminal differentiation, cellular senescence and liver diseases. Here, we review the underlying mechanism and potential biological significance of hepatocytes polyploidization during normal postnatal growth and pathologic processes, and also discuss the promise strategy of polyploidy reversal in liver disease.