Abstract
TNFRSF12A mRNA expression and the distribution of TNFRSF12A+ cells were studied in detail for the first time at different stages of fibrosis in the rat liver. Under physiological conditions, the expression level of TNFRSF12A mRNA was 0.224 (95% CI: 0.170–0.277). At the same time, cells expressing the TNFRSF12A marker were practically absent. In bridging fibrosis, the first peak of TNFRSF12A mRNA growth (p = 0.000) and an increase in the area of TNFRSF12A+ cells (p = 0.000) was established. The second peak (p = 0.000) was detected during the process of transformation of fibrosis into cirrhosis. At the stage of incomplete cirrhosis, a sharp drop was noted. A subsequent increase in the expression of TNFRSF12A mRNA and the area of TNFRSF12A+ cells was observed from the stage of significant cirrhosis. The immunohistochemical method revealed two groups of TNFRSF12A+ cells. In the sinusoidal capillaries TNFRSF12A+, the cells had a shape close to flat and resembled endotheliocytes, while in the fibrous connective tissue they were rounded. The number of α-SMA+ cells increased gradually (p = 0.000) before the onset of significant cirrhosis, and then there was a sharp increase (p = 0.000).
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This work was carried out within the framework of the state scientific research program “Basic and Applied Sciences—Medicine” of the Ministry of Health of the Republic of Belarus, task no. 2.89 “Study of the Role of the Expression of Genes of NOTCH- and TWEAK-signaling Pathways Involved in the Processes of Proliferation and Differentiation of Liver Cells in Normal Conditions and in Defeating Its Toxic State” (registration no. 20190107).
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The experimental protocol was approved at a meeting of the Commission on Bioethics and Humane Treatment of Laboratory Animals at the educational institution Vitebsk State Order of Friendship of Peoples Medical University (protocol no. 6 of January 3, 2019). All manipulations with animals were carried out in accordance with the recommendations of the Council of Europe Convention for the Conservation of Vertebrate Animals Used for Experimental and Other Scientific Purposes dated March 18, 1986; the EEC Council Directive dated November 24, 1986; and the recommendations of the FELASA Working Group Report (1994–1996).
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Lebedeva, E.I., Shchastniy, A.T. & Babenka, A.S. TNFRSF12A mRNA Expression and Distribution of TNFRSF12A+ Cells in the Rate Liver during Thioacetamide-Induced Fibrogenesis. Biol Bull Russ Acad Sci 51, 11–20 (2024). https://doi.org/10.1134/S1062359023602021
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DOI: https://doi.org/10.1134/S1062359023602021