• The role of mesenchymal stem cells and Imatinib in the process of liver fibrosis healing through CCL2-CCR2 and CX3CL1-CX3CR1 axis
  • Parisa Varjavand,1 Ardeshir Hesampour,2,*
    1. Department of Biology, Islamic Azad University Central Tehran Branch, Tehran, Iran
    2. Department of Biology, Islamic Azad University Central Tehran Branch, Tehran, Iran


  • Introduction: Perpetuated damages of liver conduce to liver fibrosis, accompanied by the aggregation of extracellular matrix. Macrophages play a critical role in this phenomenon. The CCL2-CCR2 and CX3CR1-CX3CL1 axes are main regulators of macrophage calling, liver infiltration, and differentiation. Here, using a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis, we sought to ascertain the effects of imatinib and bone marrow-derived mesenchymal stem cells (BM-MSCs) on the expression of these axis.
  • Methods: 16 Sprague-Dawley rats in four groups of healthy, liver fibrosis, imatinib-recipient, and BM-MSC-recipient were studied. Histopathology and Sirus-red were used to assess the treatment effects of planned techniques. For the purpose of identifying changes in the expression of the genes CCL2, CCR2, CX3CL1, and CX3CR1, quantitative real-time PCR was used.
  • Results: Histopathological findings showed the effect of imatinib and BM-MSCs in the amelioration of liver fibrosis. Our findings indicated that CCL2 and CCR2 expression had significantly diminished in imatinib and BM-MSCs therapies compared to the liver fibrosis group. Conversely, CX3CL1 and CX3CR1 gene expression showed an increase in both therapeutic groups than liver fibrosis groups.
  • Conclusion: The significant decrease in CCL2-CCR2 genes in both therapeutic groups suggests that BM-MSCs and imatinib might lead to a decline in inflammatory macrophages within the liver. The lower CCL2-CCR2 expression in imatinib-recipient showed the better performance in the modulation of inflammatory macrophage recruitment. The higher expression of CX3CL1 in BM-MSC-recipient showed the higher effect on and polarization of LY6Chigh (inflammatory) to LY6Clow (anti-inflammatory) macrophages, which tread a path for further investigation
  • Keywords: CCL2, CCR2, CX3CL1, CX3CR1, Liver fibrosis