DOI: https://doi.org/10.22263/2312-4156.2022.3.17
E.I. Lebedeva1, A.S. Babenka2, A.T. Shchastniy1
The potential of the fibrosis/cirrhosis transition point as a key element for studying the role of the Ttweak/Fn14 signaling pathway 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. 2022;21(3):17-26.
Abstract.
Objectives. To obtain the most detailed data on the dynamics of the mRNA level of the Tweak/Fn14 signaling pathway genes at morphologically confirmed stages of liver fibrogenesis using the Ishak K.G. semi-quantitative scale.
Material and methods. Liver fibrogenesis in Wistar rats was induced with thioacetamide at a dose of 200 mg/kg animal weight twice a week during 17 weeks. Real-time PCR was used to study the level of mRNA of the tweak and fn14 genes. Liver sections were stained with hematoxylin and eosin, as well as by the Mallory method. Fibrosis stage was assessed using the Ishak K.G. semi-quantitative scale.
Results. After three weeks of the experiment (the degree of fibrosis according to the Ishak K.G. scale corresponded to F1), a 5 times (p=0.029) increase in mRNA of the fn14 gene and a 2 times (p=0.001) decrease in mRNA of the tweak gene were observed compared with the control point.
At the terminal stages of fibrogenesis (the degree of fibrosis F4/F5, the transition of fibrosis to cirrhosis), there was a maximum increase in the level of mRNA of the fn14 gene – about 8 times (p=0.001) compared with the control point. At the same time, at the stage of cirrhosis (F5-F6), the minimum level of mRNA of the tweak gene was observed (20-fold drop, p=0.001) compared to the control point.
Conclusions. On the 9th week of the experiment, the transition of fibrosis to cirrhosis was morphologically proved. At this stage, the maximum mRNA level of the fn14 gene was observed, as well as the induction of the tweak mRNA level. A detailed study of the transition point of fibrosis to cirrhosis requires additional attention and further study. Perhaps this point will help reveal new details about the role of the Tweak/Fn14 signaling pathway in the process of chemically induced fibrogenesis. Additional studies are required to obtain even more detailed information, taking into account miRNAs, long non-coding RNAs, and other regulatory elements; epigenetic and metagenomic parameters.
Keywords: Wistar rats, liver fibrogenesis, Tweek/Fn14 signaling pathway, Ishak K.G. semi-quantitative scale, mRNA level, real-time PCR.
Funding: The research was conducted within the frames of the theme task of the 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 diff- erentiation of liver cells in the norm and in case of its toxic damage» (№ GR 20190107).
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Information about authors:
E.I. Lebedeva – Candidate of Biological Sciences associate professor of the Chair of Histology, Cytology and Embryology, Vitebsk State Order of Peoples’ Friendship Medical University, https://orcid.org/0000-0003-1309-4248
E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Elena I. Lebedeva;
A.S. Babenka – Candidate of Chemical Sciences, associate professor of the Chair of Bioorganic chemistry, Belarusian State Medical University, https://orcid.org/0000-0003-1309-4248
A.T. Shchastniy – Doctor of Medical Sciences, professor, rector, head of the Chair of Hospital Surgery with the course of the Faculty for Advanced Training & Retraining, Vitebsk State Order of Peoples’ Friendship Medical University,
https://orcid.org/0000-0003-2796-4240
