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

Ting Bo Liang, Kwan Man, Kin Wah Lee, Steven Hong Teng Tsui, Chung Mau Lo, Xiao Xu, Shu Sen Zheng, Sheung Tat Fan, John Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

62 Citations (Scopus)

Abstract

Background. The molecular mechanism of small-forsize 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)-κB (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 upregulation of ET-1 and deterioration of intracellular homeostasis reflected by down-regulation of Hsps and A20.
Original languageEnglish
Pages (from-to)673-678
Number of pages6
JournalTransplantation
Volume75
Issue number5
DOIs
Publication statusPublished - 15 Mar 2003
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation

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