Distinct intragraft response pattern in relation to graft size in liver transplantation.

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.

• 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)

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

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)