Analysis of the relationship between Cxcl12, Tweak, Notch1 and Yap1 mRNA expression in the molecular mechanisms of liver fibrogenesis

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Аннотация

Currently, data on the molecular mechanisms of fibrosis and cirrhosis of the liver do not allow us to fully understand all the stages in the development of these pathological processes. It is known that individual genes and signaling pathways do not function independently. Relations between them play a huge role in the implementation of their functions. Due to the complexity of studying this factor, information about their relationship is insufficient and often contradictory. In the present work, for the first time at different stages of thioacetamide-induced fibrosis in the liver of Wistar rats, mRNA expression of Notch1, Notch2, Yap1, Tweak (Tnfsf12), Fn14 (Tnfrsf12a), Ang, Vegfa, Cxcl12 (Sdf), Nos2, and Mmp-9 genes was studied in detail. Using factor analysis, three factors were obtained that combined highly correlated target genes with each other. The first factor includes four genes: Cxcl12 (r = 0.829, p < 0.05), Tweak (r = 0.841, p < 0.05), Notch1 (r = 0.848, p < 0.05), Yap1 (r = 0.921, p < 0.05). The second factor describes the correlations between the Mmp-9 (r = 0.791, p < 0.05) and Notch2 (r = 0.836, p < 0.05) genes. The third factor included genes 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 selected genes classified on the basis of mRNA expression levels suggest that their products have a pathogenetic relationship in the processes of fibrotic changes in the liver of toxic etiology. Undoubtedly, the results obtained are of fundamental interest and require further expansion in the study of fibrosis and cirrhosis of the liver.

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Авторлар туралы

E. Lebedeva

Vitebsk State Order of Peoples’ Friendship Medical University

Email: lebedeva.ya-elenale2013@yandex.ru
Белоруссия, Vitebsk, 210009

A. Shchastniy

Vitebsk State Order of Peoples’ Friendship Medical University

Хат алмасуға жауапты Автор.
Email: lebedeva.ya-elenale2013@yandex.ru
Белоруссия, Vitebsk, 210009

A. Babenka

Belarussian State Medical University

Email: lebedeva.ya-elenale2013@yandex.ru
Белоруссия, Minsk, 220116

D. Zinovkin

Gomel State Medical University

Email: lebedeva.ya-elenale2013@yandex.ru
Белоруссия, Gomel, 246050

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2. Fig. 1. Liver fragments of rats from the control group (a) and rats with induced cirrhosis after 3 (b), 5 (c), 9 (d), 11 (e) and 17 weeks. (f) after the start of the experiment. Mallory staining. ×40 (a, b, d, f); ×20 (c, d). a – Central vein (arrow); b – fibrous connective tissue (arrows); c – fibrous septa between the portal zones (arrows); d – false hepatic lobule (highlighted by an oval frame); e – false hepatic lobules (arrows); e – severe liver destruction.

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3. Fig. 2. Plot of extracted factors in 3D coordinates.

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4. Fig. 3. Changes in the levels of mRNA expression of the genes of the first factor when modeling fibrosis and cirrhosis of the rat liver.

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5. Fig. 4. Changes in the levels of mRNA expression of the second factor genes when modeling rat liver fibrosis and cirrhosis.

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6. Fig. 5. Changes in the levels of mRNA expression of third factor genes when modeling rat liver fibrosis and cirrhosis.

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