Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts.
Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Microarray profiles of 63 biopsies in 13 DD and 8 LD liver grafts done at serial time points (procurement, backbench and postreperfusion)were compared between groups using class comparisons, network and biological function analyses. Specific genes were validated by quantitative PCR and immunopathology. Clinical findings were also compared. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p < 0.005). Many upregulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of downregulated genes were linked to hepatic metabolism and energy pathways correlating with posttransplant clinical laboratory findings. There was significant upregulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant downregulation of metabolic pathways in LD grafts.
Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
J
J
de Jonge
S
S
Kurian
A
A
Shaked
K R
KR
Reddy
W
W
Hancock
D R
DR
Salomon
K M
KM
Olthoff
D000328:Adult; D002102:Cadaver; D016207:Cytokines / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology; D007378:Interleukins / Q000235:genetics; D008115:Liver Regeneration / Q000235:genetics*; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology*; D019520:Living Donors; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D018075:RNA, Complementary / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors
D016207:Cytokines; D018076:DNA, Complementary; D006133:Growth Substances; D007378:Interleukins; D018075:RNA, Complementary; D012313:RNA