Relationship between Genes and microRNAs Involved in the Migration of Cells from the Bone Marrow during Experimental Liver Fibrosis.

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.