Shchastniy A.T.1, Lebedeva E.I.1, Babenka A.S.2
The role of mRNA level of the Notch signaling pathway genes in induced rat liver fibrogenesis
1Vitebsk State Order of Peoples’ Friendship Medical University, Vitebsk, Republic of Belarus
2Belarusian State Medical University, Minsk, Republic of Belarus
Vestnik VGMU. 2021;20(2):25-37.
Objectives. To study the role of mRNA level of the Notch signaling pathway genes in induced rat liver fibrogenesis.
Material and methods. Fibrosis followed by the transition to liver cirrhosis in rats of Wistar line was induced with thioacetamide at a dose of 200 mg/kg of animal body weight twice a week for 17 weeks. The rats were randomized into 9 groups of 12 animals each. The mRNA level of the Notch signaling pathway genes was assessed by real-time PCR. The notch1, notch2, yap1 and hes1 genes were used as molecular targets. Microscopic analysis of histological preparations was performed using the OLYMPUS BX51 microscope. The degree of fibrosis was assessed according to the scale of Ishak K.G.
Results. The study of the classical transcription factor of the Notch signaling pathway, hes1, revealed its very low and stable activity in all studied samples. The analysis of relative dynamics of the mRNA level of the notch1, notch2, and yap1 genes made it possible to determine marked changes in their levels at the point of transition from the normal state of liver tissues to the development of fibrosis.
Conclusions. Within the framework of this study, the hes1 gene is not a target of the Notch pathway and can be used as a reference gene. The noted decrease in the mRNA level of the yap1 gene, probably, inhibits the compensatory-restorative processes in the liver, activates the stellate cells, and promotes the transformation of fibrosis into cirrhosis. In addition, it has been found that the revealed fluctuations in the mRNA levels of the notch1 and yap1 genes in relation to the starting point (there are no changes in the liver tissue) quite accurately describe the period of the onset of the transition of advanced fibrosis to cirrhosis. In this regard, they can be considered as potential markers of the transition of fibrosis to cirrhosis.
Key words: Wistar rats, thioacetamide, liver fibrogenesis, genes notch1, notch2, hes1, yap1, morphology.
Information about the sources of financing: The research was conducted within the frames of the theme task of State Research Programs (GPNI) of the Republic of Belarus «To study the role of expression of the NOTCH- and TWEAK signaling pathways genes, participating in the processes of proliferation and differentiation of liver cells in the norm and in case of its toxic damage» (№GR 20190107 of 19.02.2019).
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Information about authors:
Shchastniy A.T. – Doctor of Medical Sciences, professor of the Chair of Hospital Surgery with the course of the Faculty for Advanced Training & Retraining, rector of Vitebsk State Order of Peoples’ Friendship Medical University,
Lebedeva E.I. – Candidate of Biological Sciences, associate professor of the Chair of Histology, Cytology & Embryology, Vitebsk State Order of Peoples’ Friendship Medical University,
Babenka A.S. – Candidate of Chemical Sciences, associate professor of the Chair of Bioorganic Chemistry, Belarusian State Medical University,