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Vol 58(2024) N 1 p. 102-111; DOI 10.1134/S0026893324010060 Full Text

E.I. Lebedeva1*, A.T. Shchastniy1, A.S. Babenka2, D.A. Zinovkin3

Relationships between Cxcl12, Tweak, Notchl, and Yap mRNA Expression Levels in Molecular Mechanisms of Liver Fibrogenesis

1Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, 210009 Belarus
2Belarussian State Medical University, Minsk, 220116 Belarus
3Gomel State Medical University, Gomel, 246050 Belarus
Received - 2023-06-11; Revised - 2023-07-13; Accepted - 2023-07-14

Current data on the molecular mechanisms of liver fibrosis and cirrhosis fail to fully explain all stages of their development. Interactions between individual genes and signaling pathways are known to play an important role in their functions. However, data on their relationships are insufficient and often contradictory. For the first time, mRNA expression of Notch1, Notch2, Yap1, Tweak (Tnfsf12), Fn14 (Tnfrsf12a), Ang, Vegfa, Cxcl12 (Sdf), Nos2, and Mmp-9 was studied in detail at several stages of thioacetamide-induced liver fibrosis in Wistar rats. A factor analysis isolated three factors, which combined highly correlated target genes. The first factor included four genes: Cxcl12 (r = 0.829, p < 0.05), Tweak (r = 0.841, p < 0.05), Notch1 (r = 0.848, p < 0.05), and Yap1 (r = 0.921, p < 0.05). The second factor described the correlation between Mmp-9 (r = 0.791, p < 0.05) and Notch2 (r = 0.836, p < 0.05). The third factor included Ang (r = 0.748, p < 0.05) and Vegfa (r = 0.679, p < 0.05). The Nos2 and Fn14 genes were not included in any of the factors. The gene grouping by mRNA expression levels made it possible to assume a pathogenetic relationship between their products in the development of fibrotic changes due to liver toxicity.

liver fibrosis, liver cirrhosis, molecular mechanisms, mRNA expression, factor analysis, rats



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