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| Status |
Public on Aug 27, 2009 |
| Title |
Kidney-specific Dysfunction of the Organic Anion Transporter MRP2 (ABCC2): Functional Consequences for Renal Grafts |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Transplanting renal allografts represents the major curative treatment of chronic renal failure. Despite recent advances in immunosuppressive therapy, long-term survival of allografts remains a major clinical problem. Kidney function depends in part on transport proteins such as MRP2 (ABCC2) which facilitates renal secretion of amphiphilic exogenous and endogenous compounds. Inherited variants of genes not related to the immune system have been shown to modify the outcome after renal transplantation. We investigated whether ABCC2 gene variants in the donor kidney affect renal graft function.
A congenic rat model was established carrying a single nucleotide deletion in the ABCC2 gene. Renal cross transplantations were performed with wild type rats. Renal excretion of the MRP2 substrates bilirubin glucuronide and p-aminohippuric acid, but not morphine-6-glucuronide, was affected by the donor genotype. Moreover, proteomic analyses and transcriptional profiling revealed modified expression patterns indicative of increased oxidative stress in renal grafts carrying the mutated gene.
In the clinical part our study, we assessed ABCC2 haplotypes in renal transplant patients and evaluated graft function. The 3563T>A gene polymorphism was significantly associated with delayed graft function. Together, both experimental and clinical data show that the ABCC2 genotype of the donor kidney affects renal graft function.
Keywords: dysfunction of organic anion transporter MRP2 (ABCC2)
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| Overall design |
Performed analyses of (6) wild-type and (6) MRP2 deficient kidneys that had been transplanted in wild-type recipients.
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| Contributor(s) |
Grisk O, Steinbach AC, Ciecholewski S, Schlüter T, Klöting I, Schmidt H, Dazert E, Schaeffeler E, Steil L, Gauer S, Jedlitschky G, Schwab M, Geisslinger G, Hauser IA, Völker U, Kroemer HK, Rettig R |
| Citation(s) |
19214140 |
| Submission date |
Mar 26, 2008 |
| Last update date |
Jul 31, 2017 |
| Contact name |
Sabine Ameling |
| Organization name |
Universitätsmedizin Greifswald
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| Department |
Interfakultäres Institut für Genetik und Funktionelle Genomforschung
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| Lab |
Funktionelle Genomforschung
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| Street address |
Jahnstraße 15a
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| City |
Greifswald |
| ZIP/Postal code |
17487 |
| Country |
Germany |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (12)
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| GSM277482 |
renal-cortex_wild-type recipent_wildtype graft_repl.1 |
| GSM277483 |
renal-cortex_wild-type recipent_wildtype graft_repl.6 |
| GSM277484 |
renal-cortex_wild-type recipent_wildtype graft_repl.9 |
| GSM277485 |
renal-cortex_wild-type recipent_wildtype graft_repl.4 |
| GSM277486 |
renal-cortex_wild-type recipent_wildtype graft_repl.7 |
| GSM277487 |
renal-cortex_wild-type recipent_wildtype graft_repl.8 |
| GSM277488 |
renal-cortex_wild-type recipent_ABCC2-/- graft_repl.5 |
| GSM277489 |
renal-cortex_wild-type recipent_ABCC2-/- graft_repl.9 |
| GSM277490 |
renal-cortex_wild-type recipent_ABCC2-/- graft_repl.11 |
| GSM277491 |
renal-cortex_wild-type recipent_ABCC2-/- graft_repl.3 |
| GSM277492 |
renal-cortex_wild-type recipent_ABCC2-/- graft_repl.10 |
| GSM277493 |
renal-cortex_wild-type recipent_ABCC2-/- graft_repl.14 |
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| Relations |
| BioProject |
PRJNA107143 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10949_RAW.tar |
31.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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