Proteomic characterization of biological features in the small for size future rat liver remnant

Abstract

Small for size liver syndrome (SFSLS) may occur after extended partial hepatectomy (PH); characterized by insufficient function of the future liver remnant (FLR); biochemically demonstrated by low proconvertin-prothrombin-ratio (PP) and high bilirubin (BR). The aim of this ongoing study is to characterize differences in protein expression between different size of FLRs and to identify proteins specific for the regenerative process of minimal size FLR (MSFLR). 104 male Wistar rats subjected to 30%, 70%, or 90% PH (MSFLR in rats); SHAM or no operation. Blood and liver tissue harvested at post-operative day (POD)1, 3, and 5 (n=8 per group). Main parameters assessed: Proteomic expression by 2D-PAGE and liquid-chromatography mass-spectrometry, liver regeneration rate (RR) by change in liver weight, and serum PP and BR. 149 protein-spots were significantly different expressed between groups (FDR< 0.05, fold-change>2). By hierarchical cluster analysis 3 separate clusters formed: PH(90) POD1, POD3, POD5. Identification of the protein spots revealed 57 proteins, all specific for PH(90)-groups (up-/down-regulated compared to the other groups). RR increased significantly with size of PH. Significantly, PP was critically reduced in PH(90) at POD1 and BR elevated; both normalized at POD5. Most pronounced changes in proteomic expression after PH were found in the PH(90)-group; initially mimicking SFSLS by low PP and high BR at POD1, later recuperating liver function and growth. 57 proteins specific for PH(90)-groups were identified pending further ongoing analyses. Identification of biological factors of liver regeneration in MSFLR is important in attempt to improve outcome after extended PH and potential SFSLS.