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[Relationships between Cxcl12, Tweak, Notch1, and Yap mRNA Expression Levels in Molecular Mechanisms of Liver
E I Lebedeva1,2, A T Shchastniy1, A S Babenka3
1Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, 210009 Belarus.
Abstract:
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.
Insights
This study reveals novel gene expression patterns in thioacetamide-induced liver fibrosis. Grouping of specific genes like Notch1 and Yap1 suggests new pathways involved in fibrotic changes.
Area of Science:
- Molecular biology
- Hepatology
- Toxicology
Context:
- Liver fibrosis and cirrhosis mechanisms are not fully understood.
- Gene and signaling pathway interactions are crucial but poorly defined.
- Existing data on gene relationships in liver fibrosis are insufficient and contradictory.
Purpose:
- To investigate mRNA expression of key genes in thioacetamide-induced liver fibrosis.
- To identify correlations and potential pathogenetic relationships between genes at different fibrosis stages.
- To provide a detailed molecular understanding of liver fibrosis development.
Summary:
- mRNA expression of Notch1, Notch2, Yap1, Tweak (Tnfsf12), Fn14 (Tnfrsf12a), Ang, Vegfa, Cxcl12 (Sdf), Nos2, and Mmp-9 was analyzed in Wistar rats with induced liver fibrosis.
- Factor analysis identified three distinct gene expression groups, highlighting correlations between Cxcl12, Tweak, Notch1, Yap1; Mmp-9, Notch2; and Ang, Vegfa.
- The grouping suggests pathogenetic links between these gene products in developing liver fibrotic changes.
Impact:
- Identifies novel gene clusters potentially driving liver fibrosis.
- Offers new molecular targets for understanding and treating liver fibrosis.
- Contributes to a more comprehensive understanding of liver toxicity mechanisms.
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