Biopolym. Cell. 2019; 35(3):216-217.
Хроника и информация
Role of ERK 1/2 pathway in polyploidization of hepatocytes in cholestatic liver
1Кипароидзе С., 1Бакурадзе Е., 1Модебадзе И., 1Дзидзигури Д., 1Агагулян К.
  1. Department of Biology, Iv. Javakhishvili Tbilisi State University
    Tbilisi, Georgia

Abstract

In response to resection, the importance of cell proliferation, polyploidization and hypertrophy for liver regeneration and their contribution to rapid recovery of functions is well studied. However, relatively little information exists about liver regeneration in various pathologies where all three mechanisms mentioned above do not happen simultaneously. For example, it's established that: during alimentary dyslipidemia, mechanism of regeneration depends on the duration of hepatogenic diet uses and quality of the damage. In cholestatic liver of rat, at initial stage regeneration is only occurs by polyploidization without increasing of cells quantity. In response to trauma, increase of ploidy is also described in different mammalians tissues (heart, liver, and cornea). Based on the above, in some pathologies liver regeneration is achieved by the quantitative increase of ploidy cells, however, it is not known which signaling pathways activation/inactivation provide their appearance in each particular case. Our previous results show that inhibition of HGF receptor (C-Met) doesn’t cause the changes of polyploidization of cholestatic liver. ERK 1/2 is involved in HGF activated pathway where MEK 1 and MEK 2 are the key molecules, which can be also activated by avoiding of main receptor - C-Met. The aim of the research is the determination of role of ERK 1/2 signaling pathways in the process of hepatocytes polyplodization in cholestatic liver model. Materials and methods. Experiments were carried out on adult white rats (130-150g). Model of cholestatic liver with common bile duct ligation was used. Animals were divided into three groups: I-control intact animals, II –cholestatic animals (2nd day), III-cholestatic animals with MEK 1/2 (PD98059) inhibitor injection (10mg/kg). Nuclear DNA content was detected by using of computer software ImageJ 1.36b. Determination of colchicine mitotic index was used for assessment of proliferative activity. Results. Hepatocytes mitotic activity significantly increases on the 2nd day from common bile duct ligation in the II group. In addition, the number of diploid (2c) hepatocytes decreases and the polyploid (2c×2, 4c, 4c×2, 8c) cells are increased. In the III group of animals, the number of tetrapoloid cells (4c) has tendency to decreased, while octaploid (8c) and binuclear octoploid (4c×2) cells are not present, which is evidence for suppression of polyploidization. With regard to proliferative activity, there is no difference between the animals from II and III group. Conclusions. Inhibition of formation of high-ploidy (octaploid) cells by blocking of MEK 1/2 proteins indicates that ERK 1/2 signaling pathway is one of the necessary conditions for polyploidization of hepatocytes.