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.
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: Haley E Ramsey; Cleide G Da Silva; Christopher R Longo; Eva Csizmadia; Peter Studer; Virendra I Patel; Scott M Damrauer; Jeffrey J Siracuse; Soizic Daniel; Christiane Ferran Journal: Liver Transpl Date: 2009-11 Impact factor: 5.799
Authors: Thomas Langmann; Stefanie Ebert; Yana Walczak; Karin Weigelt; Markus U Ehrengruber; Thorsten Stiewe; Bernhard H F Weber Journal: Neuromolecular Med Date: 2009-04-14 Impact factor: 3.843
Authors: Kwan Man; Terence K Lee; Ting Bo Liang; Chung Mau Lo; Peter Chin-Wan Fung; Steven H Tsui; Xian Liang Li; Kevin T Ng; Sheung Tat Fan Journal: Ann Surg Date: 2004-07 Impact factor: 12.969
Authors: C K Sun; K T Ng; B S Sun; J W Y Ho; T K Lee; I Ng; R T P Poon; C M Lo; C L Liu; K Man; S T Fan Journal: Br J Cancer Date: 2007-06-05 Impact factor: 7.640