| 17714472 |
Asano Y, Iimuro Y, Son G, Hirano T, Fujimoto J: Hepatocyte growth factor promotes remodeling of murine liver fibrosis, accelerating recruitment of bone marrow-derived cells into the liver. Hepatol Res. 2007 Dec;37(12):1080-94. Epub 2007 Aug 20.
Aim: Hepatocyte growth factor (HGF) ameliorates liver fibrosis/cirrhosis in animal models, while the participation of bone marrow-derived cells (BMC) in the repair process of injured organs has recently been reported. In this study we investigated the roles of HGF and BMC in a remodeling process of liver fibrosis. Methods: C57BL/6 J mice were treated with carbon tetrachloride (CCl (4)) for 10 weeks. At week six, the mice underwent whole body irradiation and transplantation with bone marrow cells from syngenic LacZ-transgenic mice. After the transplantation, gene transfer of HGF into skeletal muscles was performed once a week for four weeks. In the control group, sterile saline was injected. Results: HGF gene transfer ameliorated the CCl (4)-induced liver fibrosis, accelerating recruitment of LacZ-expressing cells into the liver. This phenomenon was accompanied byincreased gelatinase activity in the liver. A large number of the LacZ-positive cells expressed markers of vascular endothelial cells, while some of them had a marker of macrophages. Expression of stromal cell-derived factor (SDF)-1 in the liver was upregulated around the central veins, especially in the HGF gene-transferred animals, recruiting chemokine (C-X-C motif) receptor (CXCR) 4-positive cells in this area. Conclusion: Transplanted BMC participate in the HGF-induced remodeling process of liver fibrosis. The roles of HGF in this process include the recruitment of BMC, possibly through increased expression of SDF-1 in part, as well as anti-apoptotic, mitogenic and antifibrotic activities on liver cells. |
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