Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat syngeneic (sTX) and allogeneic kidney (aTX) transplantation compared to control (ctr) kidneys

ABSTRACT: Microarray analyses provide a powerful approach to identify gene expression alterations following kidney transplantation. However, the heterogeneity of human kidney transplant specimens and the variation in sample preparation precludes conclusions regarding the underlying mechanisms of the observed alterations. We used a well defined experimental rat kidney transplantation model with consistent transplant and sample preparation procedures to analyze genome wide changes in gene expression after syngeneic (sTX) and allogeneic transplantation (aTX) four days after transplantation. Both interventions were associated with dramatic changes in gene expression. Genes and Pathways related to immune response were extremely up regulated after aTX. Several of the up regulated genes have been described by other groups and we are able to proof this in one study. But several genes are reported for the first time to be up regulated in expression after renal aTX. The function of these genes in acute rejection process has to be evaluated. On the other hand the up regulation of regulatory or protective genes indicates that regulatory mechanism are activated after aTX trying to down regulate the immune response or protect the tissue against the immune system. The study is capable to serve as a representative study in aTX mediated gene expression by covering the known transcriptional changes reported by other groups and identification of novel markers and pathways. Further analysis of the duplicated datasets by other groups can help for a better understanding of the mechanisms mediated by acute rejection and thereby increase the therapeutic threatment. Experiment Overall Design: Male LewisâBrown-Norway (LBN) and Lewis (LEW) rats were used in the present study. All recipients were bilaterally nephrectomized immediately before donor kidney TX. In brief, the left kidney including ureter, renal artery, a piece of aorta and renal vein was transplanted into the recipient. For the allogeneic TX (aTX) model, kidneys of LBN-rats (n=5) were transplanted into LEW-rats and for the syngeneic TX (sTX) model kidneys from LBN-rats (n=5) were transplanted into LBN-rats. The LBN-into-Lewis model leads to marked histological changes typical for acute transplant rejection. The second kidney of the LBN-donors (n=5) served as controls.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Bayram Edemir

PROVIDER: E-GEOD-6497 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Activation of counter-regulatory mechanisms in a rat renal acute rejection model.

Edemir Bayram B Kurian Sunil M SM Eisenacher Martin M Lang Detlef D Müller-Tidow Carsten C Gabriëls Gert G Salomon Daniel R DR Schlatter Eberhard E

BMC genomics 20080208

<h4>Background</h4>Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation.<h4>Results</h4>We used a rat kidney transplantation model with strict transplant and sample preparation procedures to ana ...[more]

PMID: 18261221

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Project description:Objective: Apolipoprotein E (Apo E) is a multifunctional protein, originally described in the context of lipoprotein metabolism and cardiovascular disease. More recently, anti-inflammatory functions of ApoE have been documented. ApoE was studied in the context of several inflammatory disorders, but its role in the pathogenesis of acute organ rejection is unknown. In this study, we test the hypothesis that ApoE attenuates acute renal allograft rejection. Materials and methods: The Dark Agouti (DA) to Lewis (Lew) and the Brown Norway (BN) to Lew rat strain combinations were used to investigate fatal acute rejection. In addition, Fischer 344 (F344) kidneys were transplanted to Lew rats to study reversible acute rejection. Isograft recipients and untreated Lew rats were used as controls. ApoE mRNA expression was quantified in intravascular leukocytes accumulating in the blood vessels of renal grafts and in graft tissue. Apo E protein levels were assessed in blood plasma. To test the protective potential of ApoE, recipients of BN kidneys were treated with ApoE-mimetic peptide. Results: Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression remained unchanged in the BN to Lew rat strain combination or was significantly reduced when DA rats were used as donors of the kidney. On the protein level, no changes in ApoE were seen in plasma. However, we do not know if local leukocytic ApoE expression results in increased ApoE concentrations inside graft blood vessels. Peptide treatment of allograft recipients reversed fatal rejection and significantly improved animal survival. Conclusions: ApoE plays a protective role in acute organ rejection. Further studies are needed to understand the exact mechanism how ApoE reverses acute rejection. dual-color balanced dye-swap design with 4 biological replicates, hybridized on 4 arrays

Dataset Information

Transcription profiling of rat syngeneic (sTX) and allogeneic kidney (aTX) transplantation compared to control (ctr) kidneys

Publications

Activation of counter-regulatory mechanisms in a rat renal acute rejection model.

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