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Relationship between Genes and microRNAs Involved in the Migration of Cells from the Bone Marrow during Experimental
E I Lebedeva1, A T Shchastniy2, A S Babenka3
1Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, Republic of Belarus. lebedeva.ya-elenale2013@yandex.ru.
Abstract:
Progressive toxic liver fibrosis in Wistar male rats was characterized by the migration of CX3CR1+ and CD34+ cells from the bone marrow, accompanied by a mild increase in their numbers. From weeks 3 to 5 and 9 to 13, the number of CX3CR1+ cells remained approximately the same. The area occupied by CD34+ cells increased by 2 times (p<0.001) only by the end of the experiment. At week 3, the correlation between Cxcl12 and Notch2 mRNA was lost, while at week 9, a correlation of Cxcl12 with Notch1 and Notch2 was observed. From week 11 onwards, a correlation of Cxcl12 with Notch2 was revealed and a correlation with Notch1 disappeared. miR-3558-3p was correlated with Cxcl12 mRNA level at the stages of progressive fibrosis and nodular remodeling of the liver parenchyma. The greatest number of miRNAs showed direct and inverse correlations of moderate to medium strength, with Cxcl12 gene at the stage of complete cirrhosis. The mRNA levels of Cxcl12 and Yap1 showed a significant correlation with each other throughout the experiment. This suggests that they may be involved in the process of cell migration from the bone marrow to the liver and play a role in fibrosis and cirrhosis. They could be considered as potential targets for the development of new treatments.
Insights
Bone marrow cell migration contributes to liver fibrosis and cirrhosis. Cxcl12 and Yap1 gene expression correlates with these processes, suggesting potential therapeutic targets for liver disease.
Area of Science:
- Hepatology and Molecular Biology
- Immunology and Cell Biology
Background:
- Liver fibrosis is a complex process involving inflammation and tissue remodeling.
- Cellular infiltration from bone marrow plays a role in the progression of liver damage.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying progressive liver fibrosis in a rat model.
- To identify potential molecular targets for treating liver fibrosis and cirrhosis.
Main Methods:
- Wistar male rats were subjected to a fibrosis-inducing protocol.
- Cellular markers (CX3CR1+, CD34+) and gene expression (Cxcl12, Notch1, Notch2, Yap1, miR-3558-3p) were analyzed over time.
- Correlation analysis was performed to identify relationships between molecular markers and disease progression.
Main Results:
- Bone marrow-derived CX3CR1+ and CD34+ cells migrated to the liver during fibrosis progression, with CD34+ cell area significantly increasing.
- Cxcl12 mRNA levels showed dynamic correlations with Notch1, Notch2, and miR-3558-3p throughout fibrosis development.
- A significant correlation between Cxcl12 and Yap1 mRNA was observed throughout the experiment.
Conclusions:
- Cell migration from bone marrow, modulated by Cxcl12 and Yap1, is implicated in liver fibrosis and cirrhosis.
- Cxcl12 and Yap1 represent potential therapeutic targets for mitigating liver fibrosis and cirrhosis progression.
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