Gene expression profiling of acute cellular rejection in rat liver transplantation using DNA microarrays.
Acute cellular rejection (ACR) is still a major problem in organ transplantation, and its genetic and molecular mechanisms remain poorly understood. We used DNA microarrays to investigate the gene expression profiles in ACR. We hypothesized that changes of gene expression in grafts could also be detected in peripheral blood leukocytes. We first compared the gene expression profiles in liver isografts (Lewis to Lewis) and allografts (Dark Agouti to Lewis) harvested from rats at days 1, 3, 5, and 7 after transplantation. Hierarchical clustering analysis indicated that gene expression started to change on day 3, and 89 differentially expressed genes were extracted from allografts in comparison with isografts at day 3. Most of the up-regulated genes were associated with graft-infiltrating leukocytes. We then confirmed the similarity of gene expression changes in peripheral leukocytes by quantitative real-time polymerase chain reaction. We also investigated the gene expression changes in other inflammatory and liver dysfunction models. Two interferon-gamma inducible genes, interferon regulatory factor 1 and guanylate nucleotide binding protein 2, were overexpressed in both the peripheral leukocytes and liver graft during ACR. Although further studies are necessary, these 2 genes in peripheral leukocytes could be potentially useful markers for rejection or immunosuppression.
Hama
Naoki
N
Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yanagisawa
Yuka
Y
Dono
Keizo
K
Kobayashi
Shogo
S
Marubashi
Shigeru
S
Nagano
Hiroaki
H
Umeshita
Koji
K
Watanabe
Shinya
S
Uchiyama
Yasuo
Y
Monden
Morito
M
D000208:Acute Disease; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics; D002779:Cholestasis / Q000235:genetics; D016000:Cluster Analysis; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D006084:Graft Rejection / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000235:genetics; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
C086640:Gbp2 protein, rat; D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D019204:GTP-Binding Proteins