Comparative proteome profile during the early period of small-for-size liver transplantation in rats revealed the protective role of Prdx5.
OBJECTIVE
In living-donor liver transplantation (LDLT), "small-for-size graft (SFSG) syndrome" is a complex process resulting primarily from ischemia-reperfusion injury (IRI) and portal hypertension associated with size mismatch between graft and recipient. In the early period of LDLT, molecular events related to subsequent apoptosis, necrosis, proliferation and regeneration appeared in specific protein expression patterns.


METHODS
We used 2D-PAGE and MALDI-TOF/TOF technology to construct a comparative proteome profile for small-for-size liver grafts (SFSGs) during the early period of LDLT in rats (ischemia 1h, and 2, 6, 24, 48 h post-reperfusion); sham-operated liver was the control. Western blotting was used to confirm the proteomics results and immunohistochemistry was carried out to explore the cellular localization of selected proteins. We further performed cluster and bioinformatics analyses of differential proteins. Lastly, we overexpressed Prdx5 in liver grafts using an adenoviral vector to evaluate its protective role.


RESULTS
We identified 314 differential protein spots corresponding to 259 different proteins. Cluster analyses revealed six expression patterns, and bioinformatics analyses revealed that each pattern was related to many specific cell processes. We also showed that Prdx5 overexpression could attenuate injury to SFSGs and increase survival in recipients.


CONCLUSIONS
Taken together, these results reveal an important proteome profile that is functional in SFSGs during early period of LDLT, and provide a strong basis for further research.
Wu
Jindao
J
Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Tang
Qiyun
Q
Shen
Jian
J
Yao
Aihua
A
Wang
Fuqiang
F
Pu
Liyong
L
Yu
Yue
Y
Li
Xiangcheng
X
Li
Guoqiang
G
Zhang
Feng
F
Sun
Beicheng
B
Kong
Lianbao
L
Li
Donghua
D
Zhang
Yewei
Y
Guo
Xuejiang
X
Wang
Xuehao
X
D000818:Animals; D017209:Apoptosis; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D008099:Liver / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000473:pathology / Q000502:physiology*; D019520:Living Donors; D023421:Models, Animal; D009929:Organ Size; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013577:Syndrome; D013997:Time Factors
D020543:Proteome; D011994:Recombinant Proteins; D054464:Peroxiredoxins