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GSE37838
Homo sapiens
76 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In deceased donor kidney transplantation, acute kidney injury (AKI) prioir to surgery is a major determinant of delayed graft function (DGF), but AKI is histologically silent and difficult to assess. We hypothesized that a molecular measurement of AKI would add power to conventional risk assessments to predict the early poor allograft function at first week post transplantation.
Publication Title
Comparing molecular assessment of implantation biopsies with histologic and demographic risk assessment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Tissue inhibitors of metalloproteinases (TIMP) are endogenous inhibitors of matrix metalloproteinases (MMP). While TIMP2 and TIMP3 inhibit MMPs, TIMP3 also inhibits activation of pro-MMP2 whereas TIMP2 promotes it. Here we assessed the differential role of TIMP2 and TIMP3 in renal injury using the unilateral ureteral obstruction model. Gene microarray assay showed that post-obstruction, the lack of TIMP3 had a greater impact on gene expression of intermediate, late injury- and repair-induced transcripts, kidney selective transcripts and solute carriers. Renal injury in TIMP3-/-, but not in TIMP2-/- mice increased expression of collagen type I/III, connective tissue growth factor, transforming growth factor- and the downstream Smad2/3 pathway. Interestingly, ureteral obstruction markedly increased MMP2 activation in the kidneys of TIMP3-/- mice which was completely blocked in the kidneys of TIMP2-/- mice. These changes are consistent with enhanced renal tubulointerstitial fibrosis in TIMP3-/- and its reduction in TIMP2-/- mice. The activity of tumor necrosis factor- converting enzyme, caspase-3 and mitogen activated kinases were elevated in the kidneys of TIMP3-/- but not TIMP2-/- mice, suggesting enhanced activation of apoptotic and pathological signaling pathways only in the obstructed kidney of TIMP3-/- mice. Thus, TIMP2 and TIMP3 play differential and contrasting roles in renal injury, TIMP3 protects from damage whereas TIMP2 promotes injury through MMP2 activation.
Publication Title
TIMP2 and TIMP3 have divergent roles in early renal tubulointerstitial injury.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 391 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Histologic diagnosis of T cell-mediated rejection in kidney transplant biopsies has limited reproducibility because it is based on non-specific lesions using arbitrary rules that are subject to differing interpretations. We used microarray results from 403 indication biopsies previously given histologic diagnoses to develop a molecular classifier that assigned a molecular T cell-mediated rejection score to each biopsy. Independent assessment of the biopsies by multiple pathologists confirmed considerable disagreement on the presence of TCMR features: 79-88% accuracy and 35-69% sensitivity. The agreement of the molecular T cell-mediated rejection score with the histology diagnosis was similar to agreement among individual pathologists: accuracy 89%, sensitivity 51%. However, the score also predicted the consensus among pathologists, being highest when all agreed. Many discrepancies between the scores and the histologic diagnoses were in situations where histology is unreliable e.g. scarred biopsies. The score correlated with histologic lesions and gene sets associated with T cell-mediated rejection. The transcripts most often selected by the classifier were expressed in effector T cells, dendritic cells, or macrophages or inducible by interferon-gamma. Thus the T cell-mediated rejection score offers an objective assessment of kidney transplant biopsies, predicting the consensus opinion among multiple pathologists, and offering insights into underlying disease mechanisms.
Publication Title
Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 282 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Kidney transplants that develop dysfunction or proteinuria after one year post transplant are at considerable risk for progression to renal failure. Identifying the molecules associated with graft failure could potentially lead to interventions that would slow the progression of organ failure.
Publication Title
A molecular classifier for predicting future graft loss in late kidney transplant biopsies.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers.
Publication Title
Molecular phenotypes of acute kidney injury in kidney transplants.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 304 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The authors report that in INTERCOM, a prospective international study of 300 kidney transplant biopsies, a microarray-based molecular score for T cell-mediated rejection changed the assessment of 26% of all biopsies, illustrating the potential of precision diagnostics to impact practice.
Publication Title
Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Olfaction is fundamental for survival but there is little known about the connection between smell perception and metabolism. In this study we implemented IGF1R knockout mice in the olfactory sensory neurons, by olfactory marker protetin (OMP) Cre specific recombination, and investigated metabolic parameters, smell perception and transcriptome sequencing. We could demonstrate that IGF1R knockout in the olfactory sensory neurons results in enhanced smell perception, insulin resistance under normal chow diet conditions and increased adiposity in mice fed control diet. Transcriptome analysis of the olfactory epithelium revealed differential expression of markers for mature and immature olfactory sensory neurons, being down-regulated and up- regulated respectively, pointing to differentiation-dependent changes that result in increased olfactory perception. Collectively, this study provides evidence that enhanced smell perception can result in insulin resistance and increased adiposity. Overall design: mRNA profiles of olfactory sensory neurons (OSN) extracted from homozygous tissue-specific IGF1R knockout (OMPIGF1R) and respective cotnrol mice (OMPflfl) were generated by deep sequencing, in four replicates using Illumina sequencing
Publication Title
The Sense of Smell Impacts Metabolic Health and Obesity.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These experiments aim determine the effects of Smo and Ets-2 signaling on fibroblast gene expression.
Publication Title
Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
E2F1 has been shown to induce both proliferation and apoptosis.
Publication Title
An E2F1-dependent gene expression program that determines the balance between proliferation and cell death.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profiling with microarrays was used to identify genes differentially expressed in the lungs of B6 and BALB CF mice compared to non-CF littermates
Publication Title
Strain-dependent pulmonary gene expression profiles of a cystic fibrosis mouse model.
Sample Metadata Fields
No sample metadata fields
View Samples