Comparative proteome profile during the early period of small-for-size liver transplantation in rats revealed the protective role of Prdx5

Abstract

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. 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. 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. 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.