Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Microarray expression data from human renal mesangial cells (HMC) treated with a Cyclosporine A (CsA) time course.

ABSTRACT: HMCs were treated with CsA (4.2 M-BM-5M) for 0 12 and 48 hours. To exmaine global gene changes in the renal mesangium following CsA treatment in order to identify novel contributors to CsA-induced renal dysfunction Microarray analysis was used to identify novel mechanisms of CsA nephrotoxicity in the golmerulus Glomerulosceroisis is a key component of overall CsA neophrotxocity. The mesangial cells of the glomerulus are an important cell type with the renal glomerulus. In order to delineate this complex process and identify novel mechanism of the disease and identify possible future therapeutic targets HMCs were treated with CsA for 0 (control) 12 or 48 hours. HMCs were treated with 4.2 M-BM-5M CsA and RNA extracted and hybridised on Affymetrix (HG-U133A) microarrays

ORGANISM(S): Homo sapiens

SUBMITTER: Sein O'Connell

PROVIDER: E-GEOD-30952 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling.

O'Connell Séin S Tuite Niamh N Slattery Craig C Ryan Michael P MP McMorrow Tara T

Toxicological sciences : an official journal of the Society of Toxicology 20111206 1

Cyclosporine A (CsA) is a potent immunosuppressant used to prevent organ transplant rejection and in the treatment of autoimmune diseases. However, chronic CsA nephropathy is the major limiting factor to its widespread use. The exact mechanisms of CsA-induced renal damage remain to be fully elucidated. The objective of the current research was to examine whether CsA treatment induced any glomerular mesangial cell alterations. In this research goal, human mesangial cells (HMCs) were treated with ...[more]

PMID: 22147139

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Project description:Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-specific transcript dataset (GTD) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with ‘a prior’i established known prominent glomerular expression served for validation and were all found in the novel expression library (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression for several novel glomerulus-enriched genes identified in REGGEL was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. Glomerular disease associated differential mRNA regulation of ROBO2 was found in diabetic nephropathy. In summary, using a comparative strategy on microdissected nephrons novel transcripts with predominant expression in the human glomerulus could be identified. A systematic analysis of this glomerulus-specifc gene expression library allows the detection of target molecules and biological processes involved in glomerular biology and renal disease. Sample from kidney biopsies of 6 transplant Living Donors (LD) were microdissected into tubular and glomerular compartment and separately hybridized an Affymetrix HG-U133A microarrays. Background correction and quantile normalization was ferformed using RMAexpress Version 0.3 as part of a dataset of 88 samples for glomeruli and 84 samples for tubuli. All data are reported in log2 scale. A background filter cut-off was defined to lower the count of false positive calls using the highest signal value obtained from non-human Affymetrix control oligonucleotides multiplied by a factor of 1.2, following previous studies: Schmid H, Boucherot A, Yasuda Y, et al.: Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes 55:2993-3003, 2006 A linear model was fit to compensate differences in expression due to separate sample processing of the compartments. Subsequently, genes were selected based on foldchange.

Dataset Information

Microarray expression data from human renal mesangial cells (HMC) treated with a Cyclosporine A (CsA) time course.

Publications

Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling.

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