title: Hepatocyte growth factor promotes remodeling of murine liver fibrosis, accelerating recruitment of bone marrow-derived cells into the liver.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Yasukane
authors: Y
authors: Asano
authors: Yuji
authors: Y
authors: Iimuro
authors: Gakuhei
authors: G
authors: Son
authors: Tadamichi
authors: T
authors: Hirano
authors: Jiro
authors: J
authors: Fujimoto