The effect of hepatocyte growth factor on the initiation phase of liver regeneration after cold ischemia in a rat model of small-for-size liver transplantation.
OBJECTIVE
In this study, adenovirus carrying human HGF gene (Ad-HGF) was administered to investigate whether hepatocyte growth factor (HGF) can restore liver regeneration after prolonged cold ischemia, especially during the initiation phase, in a rat model of small-for-size liver transplantation.


METHODS
A rat model was established using 30% small-for-size liver grafts. Before hand, the grafts were preserved at 4°C for 45min, 2h, 6h and 10h in UW solution. A recombinant adenoviral vector carrying HGF and Ad-HGF or adenovirus encoding enhanced green fluorescent protein (Ad-EGFP) was administered to the 10h group. Survival rates, serum levels of alanine aminotransferase, recovery of the graft weight, hepatic architecture, proliferating cell nuclear antigen (PCNA), cell signaling pathways and several immediate early genes (e.g. jun-B, c-fos) were assessed.


RESULTS
Injury to the grafts and extent of inflammation of the small grafts increased due to prolonged cold ischemia, while the number of PCNA- positive hepatocytes decreased and liver regeneration mechanism was affected. These factors resulted in low levels of interleukin (IL)-6, tumor necrosis factor receptor (TNFR)- α , and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in liver tissue. Ad-HGF administration markedly improved the survival rate, but it did not significantly affect the other parameters.


CONCLUSIONS
Prolonged cold ischemia significantly impaired the regenerative ability of small grafts. Ad-HGF promoted liver regeneration but had no observable effect on the initiation phase of liver regeneration.
Nanjing Medical University, Nanjing, Jiangsu Province, China.
Zhi Yuan
ZY
Hua
Jun
J
Song
Feng
F
Cheng
Yue
Y
Yu
Yun
Y
Gao
Aihua
A
Yao
XueHao
X
Wang
D000256:Adenoviridae; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D050377:Cold Ischemia / Q000009:adverse effects*; D015870:Gene Expression; D016762:Genes, fos; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology* / Q000293:injuries / Q000378:metabolism*; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D023421:Models, Animal; D009929:Organ Size; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D018809:Proliferating Cell Nuclear Antigen; D016755:Proto-Oncogene Proteins c-jun; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D000410:Alanine Transaminase