Human Nephrosclerosis Triggers a Hypoxia-Related Glomerulopathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE20602 | GEO | 2010/03/30
SECONDARY ACCESSION(S): PRJNA124773
REPOSITORIES: GEO
Similar Datasets
Project description:Expression data from microdissected glomeruli to examine the role of hypoxia in glomerulosclerosis of human Nephrosclerosis (NSC). Human Kidney biopsies of patients with NSC (n=14) and TN (n=4) were selected for RNA extraction and hybridization on Affymetrix microarrays. Gene expression data was then analysed using Genepattern and Genomatix software suites which revealed that CXCR4/CXCL12 plays a role in human NSC and therefore indicate that hypoxia contributes to glomerular damage in NSC. This dataset is part of the TransQST collection.
2010-03-30 | E-GEOD-20602 | biostudies-arrayexpress
Project description:In the kidney, hypoxia contributes to tubulointerstitial fibrosis, but little is known about its implications for glomerular damage and glomerulosclerosis. Chronic hypoxia was hypothesized to be involved in nephrosclerosis (NSC) or "hypertensive nephropathy." In the present study genome-wide expression data from microdissected glomeruli were studied to examine the role of hypoxia in glomerulosclerosis of human NSC. Functional annotation analysis revealed prominent regulation of hypoxia-associated biological processes in NSC, including angiogenesis, fibrosis, and inflammation. Glomerular expression levels of a majority of genes regulated by the hypoxia-inducible factors (HIFs) were significantly altered in NSC. Among these HIF targets, chemokine C-X-C motif receptor 4 (CXCR4) was prominently induced. Glomerular CXCR4 mRNA induction was confirmed by quantitative RT-PCR in an independent cohort with NSC but not in those with other glomerulopathies. By immunohistological analysis, CXCR4 showed enhanced positivity in podocytes in NSC biopsy specimens. This CXCR4 positivity was associated with nuclear localization of HIF1alpha only in podocytes of NSC, indicating transcriptional activity of HIF. As the CXCR4 ligand CXCL12/SDF-1 is constitutively expressed in podocytes, autocrine signaling may contribute to NSC. In addition, a blocking CXCR4 antibody caused significant inhibition of wound closure by podocytes in an in vitro scratch assay. These data support a role for CXCR4/CXCL12 in human NSC and indicate that hypoxia not only is involved in tubulointerstitial fibrosis but also contributes to glomerular damage in NSC.
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Project description:We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples. Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. Stringent statistical analysis using the Benjamini_Hochberg corrected 2-tailed t-test was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. This Series includes DKD and control glomeruli samples.
2011-08-02 | E-GEOD-30528 | biostudies-arrayexpress
Project description:We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples. Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. Stringent statistical analysis using the Benjamini_Hochberg corrected 2-tailed t-test was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. This Series includes control glomeruli and tubuli samples.
2011-08-02 | E-GEOD-30566 | biostudies-arrayexpress
Project description:Evidence from confocal microscopic reconstruction of maize anther development in fertile, mac1 (excess germ cells) and msca1 (no germ cells) flowers indicates that the male germ line is multiclonal and uses the MAC1 protein to organize the somatic niche. Furthermore, we identified redox status as a determinant of germ cell fate, defining a mechanism distinct from the animal germ cell lineage. Decreasing oxygen or H2O2 increases germ cell numbers, stimulates superficial germ cell formation, and rescues germinal differentiation in msca1 flowers. Conversly, oxidizing environments inhibit germ cell specification and cause ectopic differentiation in deeper tissues. We propose that hypoxia, arising naturally within growing anther tissue, acts as a positional cue to set germ cell fate. key words: anther development, maize, male-sterile Two replicates of laser microdissected pre-meiotic cells were compared to two replicates of whole anthers, which contains pre-meiotic cells and somatic cells, from the same developmental stage and individual wild type plants. In another experiment, laser microdissected pre-meiotic cells from wild type (mac1-heterozygous) anthers were compared to laser microdissected pre-meiotic cells from mac1 (mutant) anthers.
2012-07-04 | E-GEOD-39101 | biostudies-arrayexpress
Project description:We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples. Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. Stringent statistical analysis using the Benjamini_Hochberg corrected 2-tailed t-test was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. This Series includes DKD and control tubuli samples.
2011-08-02 | E-GEOD-30529 | biostudies-arrayexpress
Project description:The neural stem cell (NSC) niche controls the expansion and differentiation of NSCs. Blood vessels are part of this neurogenic niche, but their functional significance for the regulation of NSC differentiation and the mechanisms involved remain unclear. Here, we report that blood vessel formation in the developing mouse and ferret cortex coincided with induction of NSC differentiation in time and space. Moreover, selective inhibition of brain angiogenesis in vessel-specific Gpr124 null embryos caused hypoxia and increased NSC expansion at the expense of differentiation. The hypoxia-inducible factor (HIF)-1Îą mediated this process, as the level of HIF-1Îą controlled NSC differentiation. Niche blood vessels regulated NSC differentiation at least in part by providing oxygen, as exposure to increased ambient oxygen levels rescued NSC differentiation in hypoxic brains of Gpr124 deficient embryos. Our findings establish a novel oxygen-dependent mechanism of how blood vessels regulate NSC differentiation.
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Project description:Transcriptome comparison of glomeruli from kidneys with focal segmental glomerulosclerosis (FSGS) and glomeruli from the unaffected portion of tumor nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
2018-10-16 | GSE121233 | GEO
Project description:Multiple diseases are associated with a pathological hypoxia in the brain, resulting in various neurological sequalae. Understanding the response to hypoxia of neurons and neural stem cells (NSCs) will help devise better therapeutic strategies. We have exposed primary neurons (PN) and neural stem cells to 1% O2. Both cell types survived well, and neurons showed no obvious morphological changes. The NSCs, however, became fusiform, and displayed a population of cells with accelerated transition in cell cycle. Gene expression profile through microarray analysis revealed major differences in response to hypoxia between NSC and PN. Not only the number of genes significantly changes was ~five-fold higher in NSC, but the types of genes involved and the direction of change was quite different. In particular, NSCs up-regulated multiple growth factors and down-regulated most other cytokines and metalloproteases , while PN down-regulated most neuronal-specific genes, up-regulated growth factors, with no major effect on cytokines. We conclude that hypoxia 1- accelerates cell cycle transition of NSC in a post-transcriptional fashion ; 2-affects cytokines in NSC but not in neurons; 3-result in up-regulation of multiple growth factors in NSC and PN; and 4-suppresses neuronal specific functions. 1) Primary neurons (PN) and neural stem cells were exposed to 1% O2. 2) Gene expression profile through microarray analysis was used to determine the differences in response to hypoxia between NSC and PN.
2011-12-31 | E-GEOD-24131 | biostudies-arrayexpress