Open AccessAdenoviral cardiotrophin‐1 transfer improves survival and early graft function after ischemia and reperfusion in rat small‐for‐size liver transplantation model
Author(s) -
Song Jun,
Zhang YeWei,
Yao AiHua,
Yu Yue,
Hua ZhiYuan,
Pu LiYong,
Li GuoQiang,
Li XiangCheng,
Zhang Feng,
Sheng GuoQing,
Wang XueHao
Publication year - 2008
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2007.00616.x
Subject(s) - medicine , liver transplantation , transplantation , apoptosis , mapk/erk pathway , protein kinase b , cancer research , reperfusion injury , stat protein , kinase , immunology , ischemia , microbiology and biotechnology , biology , stat3 , biochemistry
Summary This study was to investigate the effect of donor liver adenoviral cardiotrophin‐1 (CT‐1) gene transfer on early graft survival and function in rat small‐for‐size liver transplantation. We constructed a recombinant murine CT‐1 adenoviral vector. Donor rats were transduced in vivo with adenoviruses expressing CT‐1 (AdCT‐1) or control vector (AdEGFP). Livers were harvested 4 days later, reduced to 40% of weight, and transplanted. A syngeneic rat orthotopic liver transplantation model was performed using 40% small‐for‐size grafts. Graft survival, liver function, hepatic architecture change, the degree of necrosis and apoptosis, and cell survival signaling pathways were assessed. AdCT‐1 pretreatment markedly improved liver function and the survival of small‐for‐size grafts. In the CT‐1 treatment group, hepatic architecture was well protected, apoptotic and necrotic cells were reduced; anti‐apoptotic protein bcl‐2 was up‐regulated and pro‐apoptotic cleaved caspase‐3 was down‐regulated, cell survival signaling pathways were activated by phosphorylation of protein kinase B (Akt), extracellular‐regulated kinase (ERK) and Signal transducer and activator of transcription‐3 (Stat‐3) after transplantation. In conclusion, donor liver adenoviral CT‐1 transfer ameliorated ischemia/reperfusion injury by decreasing hepatic necrosis and apoptosis in small‐for‐size liver transplantation, mediated in part by activation of the Akt, ERK, and Stat‐3 survival signaling pathways. These results may provide a potential clinical strategy to improve the outcome of small‐for‐size liver grafts.