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J. de Jonge (Jeroen), S. Kurian (Sunil Mathan), A. Shaked (Abraham), K.R. Reddy (Rajender), W. Hancock, D.R. Salomon (Dan) and K.M. Olthoff (Kim)

2009-04-01

Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts

Publication

Publication

American Journal of Transplantation , Volume 9 - Issue 4 p. 758- 772

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.

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Keywords Atf3 gene, CDKN1A gene, DNA microarrays, Gene expression profiling, Genomics, HBEGF gene, ICAM1 gene, IL10 gene, IL4R gene, IL6 gene, Liver regeneration, Liver transplantation, Living donation, NFKBIZ gene, Stat3 gene, adult, aged, alb gene, aqp9 gene, article, atrn gene, bcl3 gene, bcl6 gene, biosynthesis, c2 gene, c5r1 gene, calca gene, ccl18 gene, ccl2 gene, ccl20 gene, ccl4 gene, cd276 gene, cd4 gene, cell cycle, chuk gene, clinical article, cnga1 gene, controlled study, crp gene, cxcl12 gene, deceased donor, dkfzp564 gene, dpp4 gene, dusp5 gene, eif4e2 gene, elf3 gene, expression, gene function, genetic association, gsta4 gene, hepatitis, hla drb4 gene, hspa1b gene, human, human genome, human tissue, i kb kg gene, ifit1 gene, ifit3 gene, il1b gene, il1rl1 gene, il1rn gene, il8 gene, ilf2 gene, immunopathology, jun gene, klkb1 gene, lbp gene, liver biopsy, liver graft, liver metabolism, liver perfusion, liver regeneration, living donor, lta gene, male, microarray analysis, nfe2l1 gene, nfkb1 gene, nfkb2 gene, organ donor, polymerase chain reaction, priority journal, protein expression, pxmp2 gene, quantitative analysis, rab27a gene, reperfusion, ripk2 gene, saa1 gene, saa2 gene, scap1 gene, serology, socs3 gene, thbs1 gene, tlr3 gene, tnfaip3 gene, tnfsf10 gene, upregulation, zgpat gene
Persistent URL doi.org/10.1111/j.1600-6143.2009.02557.x, hdl.handle.net/1765/16240
Journal American Journal of Transplantation
Organisation Erasmus MC: University Medical Center Rotterdam
Citation
de Jonge, J., Kurian, S. M., Shaked, A., Reddy, R., Hancock, W., Salomon, D., & Olthoff, K. (2009). Unique early gene expression patterns in human adult-to-adult living donor liver grafts compared to deceased donor grafts. American Journal of Transplantation, 9(4), 758–772. doi:10.1111/j.1600-6143.2009.02557.x
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