Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat heterotopic cardiac transplants

ABSTRACT: Heterotopic cardiac transplants were constructed in male Wistar Furth (allograft donor) and ACI (host) rats. Rats were divided into three groups consisting of no treatment, treatment with a sub-therapeutic dose of cyclosporin A, and treated with combination of a sub-therapeutic dose of cyclosporin A and allochimeric peptide. The allografts were harvested at defined periods post-transplantation and RNA was harvested to monitor gene expression changes resulting from the various treatments in T-cells and in heart cells. Experiment Overall Design: There are 3 distinct treatment groups, with three timepoints in each group. Two tissue samples are isolated from each group: allograft heart tissue and T-cells, for a total of 18 samples. The no-treatment group can be considered a baseline sample set for the determination of gene expression changes resulting from the two treatments.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Malgorzata Kloc

PROVIDER: E-GEOD-15074 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.

Lisik Wojciech W Gong Yongquan Y Tejpal Neelam N Skelton Thomas S TS Bremer Eric G EG Kloc Malgorzata M Ghobrial Rafik M RM

Genesis (New York, N.Y. : 2000) 20100101 1

The MHC class I allochimeric protein containing donor-type epitopes on recipient-type heavy chains induces indefinite survival of heterotopic cardiac allografts in rats. We analyzed gene expression profile of heart allograft tissue. Mutated peptide [alpha1h1/u]-RT1.Aa that contains donor-type (Wistar Furth, WF; RT1u) immunogenic epitopes displayed on recipient-type (ACI, RT1a) was delivered into ACI recipients of WF hearts at the time of transplantation in addition to a 3 days course of oral cyc ...[more]

PMID: 19882666

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Project description:Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure, and gene expression. Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s from 1 to 36 months yielded a positive slope for sirolimus of 3.36 ml/min/year, and a negative slope for cyclosporine of –1.58 ml/min/year (p=0.008). Gene expression profiles of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival. Keywords = Cyclosporine Keywords = Sirolimus Keywords = Transplantation Keywords = DNA microarrays Keywords = calcineurin inhibitors Keywords: parallel sample. This dataset is part of the TransQST collection.

Dataset Information

Transcription profiling of rat heterotopic cardiac transplants

Publications

Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.

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