CoChat
Sign Up
Cited by 54Organ Transplantation Techniques and OutcomesLiver physiology and pathologyTransplantation: Methods and Outcomes

Unique Early Gene Expression Patterns in Human Adult-to-Adult Living Donor Liver Grafts Compared to Deceased Donor Grafts

Open access
De Jonge, J., Kurian, S., Shaked, A., Reddy, K.R., Hancock, W., Salomon, D.R., Olthoff, K.M.·2009·American Journal of Transplantation
DOI 10.1111/j.1600-6143.2009.02557.xPMC PMC2734955
Open this paper in CoChat — free accountOpen PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1600-6143.2009.02557.x

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A20 expression levels increase in deceased and living donor liver grafts hours following reperfusion.

    “its expression levels increase in deceased and living donor liver grafts hours following reperfusion (20).”

    From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [20]

    The Results section on deceased-donor grafts (page unavailable) names TNFAIP3/A20 among genes up-regulated after reperfusion. The living-donor Results section reports up-regulation of inflammatory genes but does not identify A20 as one of them; the Methods say POST biopsies were taken after reperfusion but do not establish the claimed interval of hours. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • A20 is induced in mice and humans as part of the hepatocyte's regenerative response following hepatectomy.

    “A20, a newly identified player in LR, is induced in mice and humans as part of the hepatocyte’s regenerative response following hepatectomy (15, 20).”

    From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [20]

    The Discussion describes regenerative gene-expression patterns in human liver grafts, but does not identify A20 as an induced gene. A search for A20 found it only in the References, in the title of a mouse hepatectomy study; our copy does not state that A20 is induced in mice and humans following hepatectomy. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 37

  1. [1]Olthoff KM Merion RM Ghobrial RM Abecassis MM Fair JH Fisher RA Outcomes of 385 adult-to-adult living donor liver transplant recipients: a report from the A2ALL Consortium Ann Surg 2005 242 3 314 323 discussion 323–315 16135918 PMC1357740
  2. [2]Feng S Goodrich NP Bragg-Gresham JL Dykstra DM Punch JD DebRoy MA Characteristics associated with liver graft failure: the concept of a donor risk index Am J Transplant 2006 6 4 783 790 16539636
  3. [3]Fausto N Campbell JS Riehle KJ Liver regeneration Hepatology 2006 43 2 Suppl 1 S45 53 16447274
  4. [4]Debonera F Aldeguer X Shen X Gelman AE Gao F Que X Activation of interleukin-6/STAT3 and liver regeneration following transplantation J Surg Res 2001 96 2 289 295 11266286
  5. [5]Debonera F Wang G Xie J Que X Gelman A Leclair C Severe preservation injury induces Il-6/STAT3 activation with lack of cell cycle progression after partial liver graft transplantation Am J Transplant 2004 4 12 1964 1971 15575898
  6. [6]Selzner N Selzner M Tian Y Kadry Z Clavien PA Cold ischemia decreases liver regeneration after partial liver transplantation in the rat: A TNF-alpha/IL-6-dependent mechanism Hepatology 2002 36 4 Pt 1 812 818 12297828
  7. [7]Arai M Yokosuka O Chiba T Imazeki F Kato M Hashida J Gene expression profiling reveals the mechanism and pathophysiology of mouse liver regeneration J Biol Chem 2003 278 32 29813 29818 12782638
  8. [8]Haber BA Chin S Chuang E Buikhuisen W Naji A Taub R High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes J Clin Invest 1995 95 2 832 841 7860767 PMC295564
  9. [9]Inoue H Ogawa W Ozaki M Haga S Matsumoto M Furukawa K Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo Nat Med 2004 10 2 168 174 14716305
  10. [10]Leu JI Crissey MA Craig LE Taub R Impaired hepatocyte DNA synthetic response posthepatectomy in insulin-like growth factor binding protein 1-deficient mice with defects in C/EBP beta and mitogen-activated protein kinase/extracellular signal-regulated kinase regulation Mol Cell Biol 2003 23 4 1251 1259 12556485 PMC141131
  11. [11]Li W Liang X Leu JI Kovalovich K Ciliberto G Taub R Global changes in interleukin-6-dependent gene expression patterns in mouse livers after partial hepatectomy Hepatology 2001 33 6 1377 1386 11391526
  12. [12]Morita T Togo S Kubota T Kamimukai N Nishizuka I Kobayashi T Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray J Hepatobiliary Pancreat Surg 2002 9 3 352 359 12353146
  13. [13]Nagano Y Nagahori K Yoshiro F Hamaguchi Y Ishikawa T Ichikawa Y Gene expression profile analysis of regenerating liver after portal vein ligation in rats by a cDNA microarray system Liver Int 2004 24 3 253 258 15189277
  14. [14]Fukuhara Y Hirasawa A Li XK Kawasaki M Fujino M Funeshima N Gene expression profile in the regenerating rat liver after partial hepatectomy J Hepatol 2003 38 6 784 792 12763372
  15. [15]Borozan I Chen L Sun J Tannis LL Guindi M Rotstein OD Gene expression profiling of acute liver stress during living donor liver transplantation Am J Transplant 2006 6 4 806 824 16539639
  16. [16]Conti A Scala S D’Agostino P Alimenti E Morelli D Andria B Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation Liver Transpl 2007 13 1 99 113 17192907
  17. [17]Flechner SM Kurian SM Head SR Sharp SM Whisenant TC Zhang J Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes Am J Transplant 2004 PMC2041877 15307835
  18. [18]Kurian SM Flechner SM Kaouk J Modlin C Goldfarb D Cook DJ Laparoscopic donor nephrectomy gene expression profiling reveals upregulation of stress and ischemia associated genes compared to control kidneys Transplantation 2005 80 8 1067 1071 16278587
  19. [19]Bolstad BM Irizarry RA Astrand M Speed TP A comparison of normalization methods for high density oligonucleotide array data based on variance and bias Bioinformatics 2003 19 2 185 193 12538238
  20. [20]Ashburner M Ball CA Blake JA Botstein D Butler H Cherry JM Gene ontology: tool for the unification of biology. The Gene Ontology Consortium Nat Genet 2000 25 1 25 29 10802651 PMC3037419
  21. [21]Hokeness KL Kuziel WA Biron CA Salazar-Mather TP Monocyte chemoattractant protein-1 and CCR2 interactions are required for IFN-alpha/beta-induced inflammatory responses and antiviral defense in liver J Immunol 2005 174 3 1549 1556 15661915
  22. [23]Selzner N Selzner M Odermatt B Tian Y Van Rooijen N Clavien PA ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice Gastroenterology 2003 124 3 692 700 12612908
  23. [24]Taub R Hepatoprotection via the IL-6/Stat3 pathway J Clin Invest 2003 112 7 978 980 14523032 PMC198534
  24. [26]Kuboki S Okaya T Schuster R Blanchard J Denenberg A Wong HR Hepatocyte NF-kappaB activation is hepatoprotective during ischemia-reperfusion injury and is augmented by ischemic hypothermia Am J Physiol Gastrointest Liver Physiol 2007 292 1 G201 207 16950761
  25. [27]White P Brestelli JE Kaestner KH Greenbaum LE Identification of transcriptional networks during liver regeneration J Biol Chem 2005 280 5 3715 3722 15546871
  26. [28]Berg CL Gillespie BW Merion RM Brown RS Jr Abecassis MM Trotter JF Improvement in survival associated with adult-to-adult living donor liver transplantation Gastroenterology 2007 133 6 1806 1813 18054553 PMC3170913
  27. [29]Togo S Makino H Kobayashi T Morita T Shimizu T Kubota T Mechanism of liver regeneration after partial hepatectomy using mouse cDNA microarray J Hepatol 2004 40 3 464 471 15123361
  28. [30]Strey CW Winters MS Markiewski MM Lambris JD Partial hepatectomy induced liver proteome changes in mice Proteomics 2004 4 1 8 15602770
  29. [31]Man K Lo CM Lee TK Li XL Ng IO Fan ST Intragraft gene expression profiles by cDNA microarray in small-for-size liver grafts Liver Transpl 2003 9 425 432 12682897
  30. [32]Zhong Z Schwabe RF Kai Y He L Yang L Bunzendahl H Liver regeneration is suppressed in small-for-size liver grafts after transplantation: involvement of c-Jun N-terminal kinase, cyclin D1, and defective energy supply Transplantation 2006 82 2 241 250 16858288
  31. [33]Berberat PO Friess H Schmied B Kremer M Gragert S Flechtenmacher C Differentially expressed genes in postperfusion biopsies predict early graft dysfunction after liver transplantation Transplantation 2006 82 5 699 704 16969295
  32. [34]Que X Debonera F Xie J Furth EE Aldeguer X Gelman AE Pattern of ischemia reperfusion injury in a mouse orthotopic liver transplant model J Surg Res 2004 116 2 262 268 15013365
  33. [35]Omura T Nakagawa T Randall HB Lin Z Huey M Ascher NL Increased immune responses to regenerating partial liver grafts in the rat J Surg Res 1997 70 1 34 40 9228924
  34. [36]Shiraishi M Csete ME Yasunaga C Drazan KE Jurim O Cramer DV Regeneration-induced accelerated rejection in reduced-size liver grafts Transplantation 1994 57 3 336 340 7509085
  35. [37]Fausto N Involvement of the innate immune system in liver regeneration and injury J Hepatol 2006 45 3 347 349 16854494
  36. [38]Weiss S Kotsch K Francuski M Reutzel-Selke A Mantouvalou L Klemz R Brain death activates donor organs and is associated with a worse I/R injury after liver transplantation Am J Transplant 2007 7 6 1584 1593 17430397
  37. [39]Rosa JL Bartrons R Tauler A Gene expression of regulatory enzymes of glycolysis/gluconeogenesis in regenerating rat liver Biochem J 1992 287 Pt 1 113 116 1329724 PMC1133131

Cited by

Sorted by citations

Authors
De Jonge, J., Kurian, S., Shaked, A., Reddy, K. R., Hancock, W., Salomon, D. R., & Olthoff, K. M.
Affiliations
  • Scripps Research Institute (US)
  • University of Pennsylvania (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Olthoff, K.M.
ORCID
Venue
American Journal of Transplantation
Publisher
Elsevier BV
Published
2009-04
Volume
9
Issue
4
Pages
758-772
ISSN
1600-6135 (ISSN-L)
DOI
10.1111/j.1600-6143.2009.02557.x
PMC
PMC2734955
OpenAlex
W2094629742
Cited by
54
References
2
Citations by year
2026: 4 · 2025: 5 · 2024: 4 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 2 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 5
FWCI
4.39
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Transplantation (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
Funders
  • Virginia Commonwealth University
  • Thailand Science Research and Innovation
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (U19AI063603)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK073192, R01 DK07319202)
Topics
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Keywords
living donor liver transplantation, deceased donor liver transplantation, early gene expression, liver graft, liver regeneration, hepatic metabolism, inflammatory gene expression, immune response
MeSH terms
Adult, Cadaver, Gene Expression Regulation, Growth Substances, Humans, Inflammation, Interleukins, Liver Regeneration, RNA, Tissue Donors, Liver Transplantation, Cytokines, RNA, Complementary, DNA, Complementary, Living Donors, Reverse Transcriptase Polymerase Chain Reaction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review