Abstract | 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.
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Authors | Ting-Bo Liang, Kwan Man, Terence Kin-Wah Lee, Steven Hong-Teng Tsui, Chung-Mau Lo, Xiao Xu, Shu-Sen Zheng, Sheung-Tat Fan, John Wong |
Journal | Transplantation
(Transplantation)
Vol. 75
Issue 5
Pg. 673-8
(Mar 15 2003)
ISSN: 0041-1337 [Print] United States |
PMID | 12640308
(Publication Type: Journal Article)
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Chemical References |
- DNA-Binding Proteins
- Early Growth Response Protein 1
- Egr1 protein, rat
- Endothelin-1
- HSP70 Heat-Shock Proteins
- Immediate-Early Proteins
- NF-kappa B
- Proteins
- Transcription Factors
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nos2 protein, rat
- Heme Oxygenase (Decyclizing)
- Heme Oxygenase-1
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Topics |
- Acute-Phase Reaction
- Animals
- Apoptosis
- DNA-Binding Proteins
(metabolism)
- Early Growth Response Protein 1
- Endothelin-1
(genetics)
- Gene Expression
- HSP70 Heat-Shock Proteins
(genetics)
- Heme Oxygenase (Decyclizing)
(genetics)
- Heme Oxygenase-1
- Immediate-Early Proteins
- Liver
(anatomy & histology, pathology, physiopathology)
- Liver Transplantation
- Male
- NF-kappa B
(metabolism)
- Nitric Oxide Synthase
(metabolism)
- Nitric Oxide Synthase Type II
- Organ Size
- Proteins
(genetics)
- Rats
- Rats, Inbred Lew
- Survival Analysis
- Transcription Factors
(metabolism)
- Vasoconstriction
(physiology)
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