Transcriptomics

Dataset Information

5

Gene expression profiling in rat renal allografts after prolonged cold ischemia


ABSTRACT: Ischemia/reperfusion injury (IRI) has a major impact on the long-term outcome of renal allografts. However, the mechanisms of IRI related to chronic allograft nephropathy (CAN) are still poorly understood. To address this issue, in a F344 to Lewis transplantation model of the rat, kidneys were either subjected to 20 min. or 24 hours of cold ischemia. A customized cDNA microarray representing 737 immune related genes was used for gene expression analysis after 12 hours and 6 months of engraftment. Thereby showing the 6-month graft function and histology were only moderately deteriorated following short cold ischemic time (20 min.), while prolonged ischemia (24 hrs) accelerated CAN development. Following prolonged cold ischemia already 12 hrs after engraftment about 30 genes were differentially expressed up to >20-fold. This included adhesion molecules, heat shock proteins, transcription factors and chemokines (CXCL10) associated with a strong CD68+ macrophage infiltration. Furthermore we observed a remarkable up-regulation of immunoproteasomes implying a re-organisation of the proteasome complex. This data might explain the higher incidence of alloreactivity following enhanced IRI. After 6 months, the prolonged cold ischemia of 24 hours revealed the significant induction of 4 genes: clusterin, C4, and the CCR7 ligands CCL19/21. This supported the observation of enhanced vasculopathy, humoral alloreactivity and increased tracking of MHC-II+ antigen presenting cells during CAN suggesting them as suitable novel targets for combating IRI. Keywords: transplantation, cold ischemia, inflammation, gene expression profiling Renal allografts from F344 donors were transplanted into unmodified LEW recipients. Before harvesting, grafts were perfused with University of Wisconsin solution at 4°C undergoing 20 min. (group A) or 24 hrs (group B) cold ischemia. Engrafted organs were either removed after 12 hrs (group I-A (n=3) and I-B (n=2)) or after 6 months (group II-A (n=3) and II-B (n=2)). Recipient animals of the group II received CyA treatment for 10 days at a dosage of 1.5 mg/kg. Untreated normal kidneys from F344 rats served as control. RNA from transplanted and untreated (control) rat kidneys were labeled by reverse transcription with Cy5 and Cy3 fluorescence, respectively.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: K Kotsch  U Janssen  B Gerstmayer  S G Tullius  A Dernier  U Kuckelkorn  Bernhard Gerstmayer  A Reutzel-Selke  R Klemz  P N Martins  H- D Volk 

PROVIDER: E-GEOD-4441 | ArrayExpress | 2010-06-25

SECONDARY ACCESSION(S): GSE4441PRJNA94709

REPOSITORIES: GEO, ArrayExpress

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Publications

Heme oxygenase-1 ameliorates ischemia/reperfusion injury by targeting dendritic cell maturation and migration.

Kotsch Katja K   Martins Paulo N A PN   Klemz Roman R   Janssen Uwe U   Gerstmayer Bernhard B   Dernier Annelie A   Reutzel-Selke Anja A   Kuckelkorn Ulrike U   Tullius Stefan G SG   Volk Hans-Dieter HD  

Antioxidants & redox signaling 20071201 12


Ischemia/reperfusion injury (IRI) has a major impact on short- and long-term renal allograft survival by increasing graft immunogenicity. Donor preconditioning by inducing heme oxygenase 1 (HO-1) has been proven to exert cytoprotective and antiinflammatory effects on the graft, thus resulting in reduced graft immunogenicity. The study analyzed the effects and mechanisms of HO-1-mediated cytoprotection in rat kidney transplants exposed to cold preservation. We studied the differential gene-expres  ...[more]

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