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The endothelial landscape and its role in von Hippel-Lindau disease

ABSTRACT: The endothelial landscape and its role in von Hippel-Lindau disease

PROVIDER: PRJNA751917 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15340526.fastq.gz	Fastqsanger.gz
	SRR15340527.fastq.gz	Fastqsanger.gz
	SRR15340528.fastq.gz	Fastqsanger.gz
	SRR15340529.fastq.gz	Fastqsanger.gz
	SRR15340530.fastq.gz	Fastqsanger.gz

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Effect of deletion of von-Hippel-Lindau (VHL) in the proximal tubule in diabetic kidney disease

Project description:To establish the role of proximal tubular hypoxia in diabetic kidney disease, we use a mouse line with a specific deletion of von-Hippel-Lindau (VHL) in the proximal tubule and treat them with streptozotocin (STZ) to induce a type I diabetes mellitus. 10 weeks after induction of diabetes mellitus samples were collected.

2022-08-08 | GSE210401 | GEO

RNA expression data from glomeruli lacking von Hippel-Lindau protein in podocytes

Project description:We and others have previously shown that glomerular endothelial cells and podocytes express hypoxia-inducible transcription factors (HIFs). HIFs bind to hypoxia response elements in target genes, such as vascular endothelial growth factor, which is continually produced by podocytes throughout life. To further assess function of HIFs in podocyte biology, podocin-Cre mice were mated with floxed von Hippel-Lindau (VHL) mice to selectively delete VHL, a component of an E3 ligase complex responsible for degradation of HIFs in normoxia. We reasoned that cells lacking VHL would overexpress stable HIFs and upregulate hypoxia-responsive genes. Progeny from these crosses displayed two phenotypes, non-proteinuric with glomerular basement membrane (GBM) defects and proteinuric with GBM defects and end-stage renal failure at ~6 months of age. Gene changes associated with the mild, non-proteinuric phenotype were studied using isolated glomeruli from wildtype and Pod-Cre fVHL mice.

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RNA expression data from glomeruli lacking von Hippel-Lindau protein in podocytes

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RNA expression data from kidneys lacking von Hippel-Lindau (VHL) protein in tubular epithelial cells

Project description:The cellular response to low oxygen supply is mediated by hypoxia-inducible factors (HIF). Under hypoxic conditions, HIF is stabilized and target genes are induced. Under normoxia, however, HIF is ubiquitinated through the von Hippel-Lindau protein (VHL), which results in proteasomal degradation. HIF activation leads to induction of genes involved in erythropoiesis, angiogenesis, and cell survival. Furthermore, HIF orchestrates a metabolic shift from oxidative phosphorylation to glycolysis to facilitate ATP production under low oxygen conditions. We used microarrays to detail gene expression changes in kidneys with stable HIF activation in renal tubules, which was achieved by tubule-specific VHL ablation.

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Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans

Project description:The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated a subunits of hypoxia-inducible factor (HIF). Although studies of VHL defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways that are distinct from HIF. Here, we report on a genetic analysis of HIF dependent and independent effects of VHL inactivation by studying gene expression patterns in C. elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1 independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17 and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1 independent function of VHL-1 that is connected with extracellular matrix function. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Bishop T, Lau KW, Epstein AC, Kim SK, Jiang M, O'rourke D, Pugh CW, Gleadle JM, Taylor MS, Hodgkin J, Ratcliffe PJ, Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans., Bishop T, et al. (2004) PLoS Biol 2(10):e289, 2004-10-01, http://biology.plosjournals.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020289 Computed

2005-07-20 | E-GEOD-2963 | biostudies-arrayexpress

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Project description:Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis

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