Lebedeva E I, Shchastniy A T, Babenka A S, Zinovkin D A, Nadyrov E A
Vitebsk State Order of Peoples' Friendship Medical University, Vitebsk, Republic of Belarus.
Belarusian State Medical University, Minsk, Republic of Belarus.
Bull Exp Biol Med. 2025 Jan;178(3):351-359. doi: 10.1007/s10517-025-06335-9. Epub 2025 Feb 13.
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.
Wistar雄性大鼠进行性毒性肝纤维化的特征是CX3CR1和CD34细胞从骨髓迁移，且其数量略有增加。在第3至5周以及第9至13周，CX3CR1细胞数量大致保持不变。仅在实验结束时，CD34细胞所占面积增加了2倍（p<0.001）。在第3周时，Cxcl12与Notch2 mRNA之间的相关性消失，而在第9周时，观察到Cxcl12与Notch1和Notch2存在相关性。从第11周起，揭示了Cxcl12与Notch2的相关性，与Notch1的相关性消失。miR-3558-3p在肝实质进行性纤维化和结节重塑阶段与Cxcl12 mRNA水平相关。在完全肝硬化阶段，大多数miRNA与Cxcl12基因呈现出中等强度的直接和反向相关性。在整个实验过程中，Cxcl12和Yap1的mRNA水平彼此呈现出显著相关性。这表明它们可能参与了细胞从骨髓迁移至肝脏的过程，并在纤维化和肝硬化中发挥作用。它们可被视为开发新治疗方法的潜在靶点。
