Intermittent dosing of G-CSF to ameliorate carbon tetrachloride-induced liver fibrosis in mice.
On the basis of the recent report that granulocyte colony-stimulating factor (G-CSF) administration after rats' partial orthotopic liver transplantation greatly improved survival rate and liver regeneration of partial graft, we here evaluated the effect of intermittent administration of G-CSF on fibrosis formation induced by carbon tetrachloride (CCl(4)). Bone marrow chimeric female C57BL/6 mice were treated with G-CSF at days 1, 7, 14, 21, and 28 after CCl(4) challenge. At day 35 after CCl(4) administration, we found that G-CSF treatment significantly reduced CCl(4)-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers in mice receiving G-CSF administration after CCl(4) challenge were significantly lower compared to those of control mice. Histological examination suggested that hepatic damage recovery was much better in these G-CSF-treated mice. Immunofluorescence and fluorescence in situ hybridization (FISH) analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology and expressed albumin, although at low frequency. These results suggest that intermittent G-CSF treatment might initiate endogenous hepatic tissue regeneration in response to CCl(4) injury and ameliorate its fibrogenic effects.
Fang
Baijun
B
Department of Haematology, Center of Excellence in Tissue Engineering, Henan Tumor Hospital, Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, China.
Luo
Suxia
S
Song
Yongping
Y
Li
Ning
N
Li
Huixiang
H
Zhao
Robert Chunhua
RC
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology* / Q000517:prevention & control*; D017690:Cell Transplantation; D003114:Colony-Forming Units Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D006909:Hydroxyproline