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| Status |
Public on Mar 30, 2007 |
| Title |
Molecular Evidence of Injury and Inflammation in Normal and Fibrotic Renal Allografts One Year Post-Transplant |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Introduction. Factors contributing to kidney transplant fibrosis remain incompletely understood—particularly in the absence of acute complications.
Methods. Baseline and one-year surveillance biopsies from 15 uncomplicated living donor kidney transplants were subjected to microarray and quantitative RT-PCR (qRT-PCR) analyses in order to examine changes in gene expression patterns over time. Biopsy pairs were purposefully selected from allografts with no history of acute complications and were divided into those that were histologically normal (n = 7) and those that had developed subclinical interstitial fibrosis (n = 8) at 1 year.
Results. Compared to the paired baseline specimens, expression levels of 3578 probesets were found altered in all the one-year biopsies studied. A large proportion of the upregulated genes in this transplant-associated profile were functionally linked with inflammation, immunity or response to injury. These included components of inflammation-related signaling pathways (integrin, interferon and TLR) as well as individual mediators of inflammatory and immune responses. An additional 2884 probesets demonstrated altered expression in fibrotic grafts only at 1 year. The gene products in this fibrosis-associated profile were also predominantly linked with inflammation and immune function, suggesting exaggerated inflammatory activity within the fibrotic grafts. qRT-PCR analyses confirmed the predicted expression patterns for selected transcripts from the microarray profiles.
Conclusions. Transcriptional profiles of histologically normal living donor renal allografts indicate that there is ongoing injury response and inflammation at 1 year compared to the immediate post-transplant period. Subclinical development of interstitial fibrosis during the first post-transplant year is associated with additional upregulation of inflammation-related genes.
Keywords: time course, comparative expression
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| Overall design |
We analyzed gene expression from a group of 15 renal transplant patients. All patients had histologically normal time zero biopsy but while 7 remained histologically normal (TxNorm), 8 developed subclinical interstitial fibrosis (GIF/TA) by 1 year. Patient groups were carefully selected to include patients on the same immunosuppresion therapy, transplant type, biopsy histology and absence of overt post-transplant complications (acute rejection, BK, etc).
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| Contributor(s) |
Park WD, Griffin M, Grande JP, Cosio F, Stegall MD |
| Citation(s) |
17397532 |
| Submission date |
Mar 28, 2007 |
| Last update date |
Aug 15, 2021 |
| Contact name |
Walter Park |
| E-mail(s) |
park.walter@mayo.edu
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| Organization name |
Mayo Clinic
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| Street address |
200 1st ST SW
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| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55901 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (30)
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| GSM178455 |
Subclinical interstitial fibrosis (GIF#1 T=0) |
| GSM178456 |
Subclinical interstitial fibrosis (GIF#1 T=12m) |
| GSM178457 |
Normal (Norm#1 T=0) |
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| Relations |
| BioProject |
PRJNA97877 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE7392_RAW.tar |
158.9 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data provided as supplementary file |
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