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Microarray and bioinformatics analysis of gene expression in experimental membranous nephropathy.

ABSTRACT: Passive Heymann nephritis (PHN), the best characterized animal model of experimental membranous nephropathy, is characterized by subepithelial immune deposits, podocyte foot processes effacement and massive proteinuria beginning 4 days following disease induction. Although single genes involved in PHN have been studied, no whole genome-wide expression analysis of kidney tissue has been performed.Microarray analysis was performed to identify gene expression changes in PHN rat kidneys during the onset of proteinuria.Our results showed that 234 transcripts were differentially expressed in diseased animals compared to controls. Genes exclusively upregulated in diseased animals were mainly required for cell structure and motility, immunity and defense, cell cycle, and developmental processes. The single most increased gene was transgelin (Tagln) showing a 70-fold upregulation in animals with PHN. Protein-protein interaction analysis revealed the following four processes of major relevance in disease manifestation: (i) DNA damage and repair; (ii) changes in the extracellular matrix; (iii) deregulation of cytokines and growth factors, as well as (iv) rearrangements of the cytoskeleton.We show for the first time the complex interplay between multiple different genes in experimental membranous nephropathy, supporting a role for genomic approaches to better understanding and defining specific disease processes.

SUBMITTER: Hauser PV

PROVIDER: S-EPMC3860588 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Microarray and bioinformatics analysis of gene expression in experimental membranous nephropathy.

Hauser Peter V PV Perco Paul P Mühlberger Irmgard I Pippin Jeffrey J Blonski Mary M Mayer Bernd B Alpers Charles E CE Oberbauer Rainer R Shankland Stuart J SJ

Nephron. Experimental nephrology 20090418 2

<h4>Background</h4>Passive Heymann nephritis (PHN), the best characterized animal model of experimental membranous nephropathy, is characterized by subepithelial immune deposits, podocyte foot processes effacement and massive proteinuria beginning 4 days following disease induction. Although single genes involved in PHN have been studied, no whole genome-wide expression analysis of kidney tissue has been performed.<h4>Methods</h4>Microarray analysis was performed to identify gene expression chan ...[more]

PMID: 19390219

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Project description:The etiology of idiopathic membranous nephropathy (IMN) is considered to be closely associated with immunoregulation and genetic factors. Circular RNAs (circRNAs) have been found to regulate gene expression in various organisms, and to play an important role in multiple physiological and pathological processes, which may be involved in the pathogenesis of IMN. The purpose of the present study was to investigate the potential relationship between circRNAs in peripheral blood and disease. The diagnoses of IMN were confirmed using electron microscopy and immunofluorescence. Total RNA was isolated and microarray analysis was used to detect the expression levels of circRNAs in the peripheral blood of patients with IMN and in normal subjects. Selected genes from the microarray were selected and verified by reverse transcription?quantitative (RT?q)PCR. Bioinformatics tools were applied for further functional evaluation, and the potential disease predictability of circRNAs was determined using receiver?operating characteristic (ROC) curves. The results showed that a total of 955 differentially expressed circRNAs were found in blood samples, 645 of which were upregulated and 310 which were downregulated. In total, five candidate circRNAs were validated using RT?qPCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified numerous types of target genes and their corresponding microRNAs (miRNAs). The miRNAs identified were involved in biological processes and enriched in multiple important pathways, including the mitogen?activated protein kinase, transforming growth factor?? and Ras signaling pathways. The levels of circ_101319 were significantly higher (P<0.001) and exhibited promising diagnostic value in patients with IMN (area under ROC =0.89). The co?expression network constructed for circ_101319 indicated that it may be associated with membranous nephropathy?related pathways by mediating miRNAs. In conclusion, the present study revealed the expression and functional profile of differentially expressed circRNAs in the peripheral blood of patients with IMN, and provided new perspectives to predict and elucidate the development of IMN.

Project description:BackgroundThe completion of the sequencing of human, mouse and rat genomes and knowledge of cross-species gene homologies enables studies of differential gene expression in animal models. These types of studies have the potential to greatly enhance our understanding of diseases such as liver cancer in humans. Genes co-expressed across multiple species are most likely to have conserved functions. We have used various bioinformatics approaches to examine microarray expression profiles from liver neoplasms that arise in albumin-SV40 transgenic rats to elucidate genes, chromosome aberrations and pathways that might be associated with human liver cancer.ResultsIn this study, we first identified 2223 differentially expressed genes by comparing gene expression profiles for two control, two adenoma and two carcinoma samples using an F-test. These genes were subsequently mapped to the rat chromosomes using a novel visualization tool, the Chromosome Plot. Using the same plot, we further mapped the significant genes to orthologous chromosomal locations in human and mouse. Many genes expressed in rat 1q that are amplified in rat liver cancer map to the human chromosomes 10, 11 and 19 and to the mouse chromosomes 7, 17 and 19, which have been implicated in studies of human and mouse liver cancer. Using Comparative Genomics Microarray Analysis (CGMA), we identified regions of potential aberrations in human. Lastly, a pathway analysis was conducted to predict altered human pathways based on statistical analysis and extrapolation from the rat data. All of the identified pathways have been known to be important in the etiology of human liver cancer, including cell cycle control, cell growth and differentiation, apoptosis, transcriptional regulation, and protein metabolism.ConclusionThe study demonstrates that the hepatic gene expression profiles from the albumin-SV40 transgenic rat model revealed genes, pathways and chromosome alterations consistent with experimental and clinical research in human liver cancer. The bioinformatics tools presented in this paper are essential for cross species extrapolation and mapping of microarray data, its analysis and interpretation.

Project description:Background/aimsDiabetic nephropathy (DN) is one of the main causes of end-stage kidney disease worldwide. Emerging studies have suggested that its pathogenesis is distinct from nondiabetic renal diseases in many aspects. However, it still lacks a comprehensive understanding of the unique molecular mechanism of DN.MethodsA total of 255 Affymetrix U133 microarray datasets (Affymetrix, Santa Calra, CA, USA) of human glomerular and tubulointerstitial tissues were collected. The 22 215 Affymetrix identifiers shared by the Human Genome U133 Plus 2.0 and U133A Array were extracted to facilitate dataset pooling. Next, a linear model was constructed and the empirical Bayes method was used to select the differentially expressed genes (DEGs) of each kidney disease. Based on these DEG sets, the unique DEGs of DN were identified and further analyzed using gene ontology and pathway enrichment analysis. Finally, the protein-protein interaction networks (PINs) were constructed and hub genes were selected to further refine the results.ResultsA total of 129 and 1251 unique DEGs were identified in the diabetic glomerulus (upregulated n = 83 and downregulated n = 203) and the diabetic tubulointerstitium (upregulated n = 399 and downregulated n = 874), respectively. Enrichment analysis revealed that the DEGs in the diabetic glomerulus were significantly associated with the extracellular matrix, cell growth, regulation of blood coagulation, cholesterol homeostasis, intrinsic apoptotic signaling pathway and renal filtration cell differentiation. In the diabetic tubulointerstitium, the significantly enriched biological processes and pathways included metabolism, the advanced glycation end products-receptor for advanced glycation end products signaling pathway in diabetic complications, the epidermal growth factor receptor (EGFR) signaling pathway, the FoxO signaling pathway, autophagy and ferroptosis. By constructing PINs, several nodes, such as AGR2, CSNK2A1, EGFR and HSPD1, were identified as hub genes, which might play key roles in regulating the development of DN.ConclusionsOur study not only reveals the unique molecular mechanism of DN but also provides a valuable resource for biomarker and therapeutic target discovery. Some of our findings are promising and should be explored in future work.

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Microarray and bioinformatics analysis of gene expression in experimental membranous nephropathy.

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Microarray and bioinformatics analysis of gene expression in experimental membranous nephropathy.

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