Proteomic analysis of differentially expressed proteins in rat liver allografts developed acute rejection.
BACKGROUND
Acute rejection (AR) after liver transplantation is a cell-mediated immune response that takes place within the allograft and results in graft dysfunction and failure, but the molecular mechanisms about hepatocyte dysfunction remain poorly understood. Here we characterized global protein expression changes in liver allograft during AR.


METHODS
The effect of an alloantigen-dependent immunological response was evaluated by syngeneic and allogeneic rat orthotopic liver transplantation (OLT). Using a combination of two-dimensional gel electrophoresis and mass spectrometry, we identified 18 differentially expressed proteins in AR allograft compared with matched tolerance allograft. Serum chemistry and allograft histology were determined.


RESULTS
Allogeneic OLT recipients exhibited elevated plasma levels of liver injury markers, progressive portal and venous inflammation and cellular infiltration in liver allograft compared with syngeneic OLT. 18 protein expressions altered by AR play important roles in metabolism, oxidative stress defense, signal transduction, biotransformation and transport. Decreased expression of protein disulfide isomerase in AR allograft was confirmed by Western blotting and immunohistochemistry.


CONCLUSIONS
This study uncovered new mechanistic insights into graft dysfunction in AR of liver allograft. Several significantly altered protein expressions act coordinately in hepatocyte dysfunction by depressed energy, enhanced oxidative stress-induced molecular damage and restrained biotransformation. The present findings may open new avenues for the understanding and prevention of graft dysfunction and failure during AR.
Cheng
J
J
Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, and Key Laboratory of Organ Transplantation, Zhejiang Province, Division of Hepatobiliary Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Zhou
L
L
Jiang
J W
JW
Qin
Y S
YS
Xie
H Y
HY
Feng
X W
XW
Gao
F
F
Zheng
S S
SS
D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014184:Transplantation, Homologous
D019704:Protein Disulfide-Isomerases