Distinct intragraft response pattern in relation to graft size in liver transplantation.
BACKGROUND
The molecular mechanism of small-for-size graft injury remains unclear. The aim of this study is to investigate the gene expression pattern of acute phase response in relation to graft size in a rat-liver transplantation model.


METHODS
A rat orthotopic liver transplantation model using 30%, 50%, and whole grafts was used. The graft survival rates and liver morphology were compared among the three groups. Two transcription factors, nuclear factor (NF)-kappaB (p65) and early growth response (Egr-1), and their downstream genes were compared.


RESULTS
According to the graft size, the rats were grouped as follows: group 1 (n=20), 32% (24-47%); group 2 (n=10), 56% (50-65%); and group 3 (n=10), 104% (89-120%). The 7-day survival rates were 20% (P=0.039 vs. group 2, P=0.000 vs. group 3), 60%, and 100% in groups 1, 2, and 3, respectively. Dilation of hepatic sinusoids and vacuolization of hepatocytes were observed in group 1. Up-regulation of Egr-1 and endothelin (ET)-1 and over-expression of nitric oxide synthase (iNOS) was found in group 1, but heme oxygenase (HO)-1 and A20 were down-regulated. At 24 hours after reperfusion, the intragraft protein level of heat-shock protein (Hsp)-70 was significantly lower in group 1 than that in group 3 (12.4 vs. 17.0 ng/mL, P=0.04). More apoptotic nuclei were found in group 1.


CONCLUSIONS
Small-for-size graft injury was related to early over-expression of Egr-1 associated with up-regulation of ET-1 and deterioration of intracellular homeostasis reflected by down-regulation of Hsps and A20.
Liang
Ting-Bo
TB
Centre for the Study of Liver Disease, The University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong SAR, China.
Man
Kwan
K
Kin-Wah Lee
Terence
T
Hong-Teng Tsui
Steven
S
Lo
Chung-Mau
CM
Xu
Xiao
X
Zheng
Shu-Sen
SS
Fan
Sheung-Tat
ST
Wong
John
J
D000210:Acute-Phase Reaction; D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000378:metabolism; D051766:Early Growth Response Protein 1; D019332:Endothelin-1 / Q000235:genetics; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D017874:Immediate-Early Proteins; D008099:Liver / Q000033:anatomy & histology* / Q000473:pathology / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009929:Organ Size; D011506:Proteins / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D019332:Endothelin-1; D018840:HSP70 Heat-Shock Proteins; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D011506:Proteins; D014157:Transcription Factors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1