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Gene expression profiling of acute cellular rejection in rat liver transplantation using DNA microarrays
Author(s) -
Hama Naoki,
Yanagisawa Yuka,
Dono Keizo,
Kobayashi Shogo,
Marubashi Shigeru,
Nagano Hiroaki,
Umeshita Koji,
Watanabe Shinya,
Uchiyama Yasuo,
Monden Morito
Publication year - 2009
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21708
Subject(s) - gene expression , liver transplantation , gene , gene expression profiling , dna microarray , transplantation , medicine , immunology , immunosuppression , fold change , real time polymerase chain reaction , biology , microbiology and biotechnology , genetics , surgery
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. Liver Transpl 15:509–521, 2009. © 2009 AASLD.