Whole heart response to stable HIF-1alpha overexpression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Chad Walton
PROVIDER: E-GEOD-12673 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:An oxygen stable form of HIF-1alpha was overexpressed in the hearts of mice, under tet-off control.
2008-12-02 | GSE12673 | GEO
Project description:In this project we explore the role of the master hypoxia regulator, Hypoxia inducible factor-1alpha (Hif-1a), in governing cardiac fibroblast (CF) function in homeostasis. CF-specific Hif-1a conditional knockout (cKO) mice were generated by breeding Pdgfra-merCremer (PdgfraMCM/+) Cre recombinase driver mice with Hif-1a-floxed mice (Hif-1aflox/). In Hif-1afl/-; PdgfraMCM/+ progeny, Hif-1a could be conditionally deleted in adult CFs by tamoxifen (tam) administration. We also introduced a Cre-dependent R26tdTomato reporter allele allowing marking of Pdgfra+ CFs and their progeny. In this experiment, we performed bulk RNA sequencing (RNA-seq) on tdTomato+ cells from the hearts of healthy cKO or heterozygous (HET) adult, male mice.
2021-11-11 | E-MTAB-9674 | biostudies-arrayexpress
Project description:In this project we explore the role of the master hypoxia regulator, Hypoxia inducible factor-1alpha (Hif-1a), in governing cardiac fibroblast (CF) function in homeostasis and following an acute ischaemic injury - myocardial infarction (MI). CF-specific Hif-1a conditional knockout (cKO) mice were generated by breeding Pdgfra-merCremer (PdgfraMCM/+) Cre recombinase driver mice with Hif-1a-floxed mice (Hif-1aflox/). In Hif-1afl/-; PdgfraMCM/+ progeny, Hif-1a could be conditionally deleted in adult CFs by tamoxifen (tam) administration. We also introduced a Cre-dependent R26tdTomato reporter allele allowing marking of Pdgfra+ CFs and their progeny. In this experiment, we first performed single-cell RNA sequencing (scRNA-seq) on tdTomato+ cells from the hearts of healthy cKO or heterozygous (HET) adult, male mice using the 10x Genomics Chromium system. We also performed scRNA-seq on tdTomato+/CD31-/CD45- cells from the hearts of cKO or HET mice at day-3 post-sham or -MI surgery.
2021-11-11 | E-MTAB-9583 | biostudies-arrayexpress
Project description:Mice deficient in Apolipoprotein E (Apoe E(-/-)) vs wild type mice were exposed to diesel engine particulate by single dose intratracheal instillation. The transcript-level response of the hearts after 24h and of the lungs after 24 h were subsequently analyzed by the 2-color microarray method. Keywords: stress response, disease state analysis Three mice of the Apo E (-/-) strain were exposed to diesel engine particulate from the National Institute of Standards and Technology via intratracheal instillation. Controls consisted of 3 littermates exposed to saline vehicle. Similarly, three wild type mice were similarly exposed to diesel particulate and three to vehicle control. 24 hours after exposure, mice were humanely sacrificed by carbon dioxide asphyxiation and the hearts and lungs were collected and frozen for analysis of total RNA. In each biological replicate, 2 color microarrays were utilized to compare pooled RNA representing all three animals of each strain, and in each condition and in each tissue; each biological replicate was performed with a dye reversal. Biological replicates of the wild type mice responses to diesel engine particulate were performed three times for heart and lung.
2010-06-23 | E-GEOD-17331 | biostudies-arrayexpress
Project description:Investigation whether hypoxic stabilization of HIF-1alpha quantitatively or qualitatively modifies the gene expression pattern induced by poly I:C, a TLR ligand that does not induce normoxic HIF-1alpha stabilization on its own (non-HIF-1alpha-stabilizing TLR ligand). Keywords: Comparison of single and combined treatment Bone marrow derived Dendritic Cells from mice were stimulated under normoxic or hypoxic conditions for 16h with media or poly I:C. Total cellular RNA was harvested, labeled and hybridised to Affymetrix Mouse Gene ST 1.0 GeneChips. Cel files were normalized with RMA.
2011-06-28 | E-GEOD-24995 | biostudies-arrayexpress
Project description:DNA Topoisomerase I inhibition by Camptothecin (CPT) derivatives can impair the hypoxia-induced cell transcriptional response. In the present work, we determined molecular aspects of the mechanism of CPT effects on HIF-1alpha activity in human cancer cells. In particular, we provide evidence that low concentrations of CPT, without interfering with HIF-1alpha mRNA levels, can reduce HIF-1alpha protein expression and activity. As luciferase assays demonstrated the involvement of the HIF-1alpha mRNA 3M-^RUTR in CPT-induced impairment of HIF-1alpha protein regulation, we performed microarray analysis to identify CPT-induced modification of miRNAs targeting HIF-1alpha mRNA under hypoxic-mimetic conditions. The selected miRNAs were then further analyzed demonstrating a role for miR-17-5p and miR-155 in HIF-1alpha protein expression after CPT treatments. The present findings establish miRNAs as key factors in a molecular pathway connecting Top1 inhibition and human HIF-1alpha protein regulation and activity, widening the biological and molecular activity of CPT derivatives and the perspective for novel clinical interventions.
2013-12-02 | E-MTAB-2022 | biostudies-arrayexpress
Project description:Human renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha, depending on VHL genotype and other events. Here, we have divided a series of RCC samples for HIF-alpha expression and VHL genotype, in order to define differentially expressed genes Keywords: Patient Sample Study A total of 57 frozen RCC samples were stained for HIF-1alpha and HIF-2alpha, and genotyped for VHL. 5 VHL WT/HIF-negative, 8 VHL-deficient/HIF-1alpha+/HIF-2alpha+ and 8 VHL-deficient/HIF-2alpha+ tumors were selected for microarray
2008-12-27 | E-GEOD-11904 | biostudies-arrayexpress
Project description:Human renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha, depending on VHL genotype and other events. Here, we have divided a series of RCC samples based on HIF-alpha expression, in order to examine levels of genomic DNA aberration. Keywords: Patient Sample Study A total of 57 frozen RCC samples were stained for HIF-1alpha and HIF-2alpha, and genotyped for VHL. 10 VHL-deficient/HIF-1alpha+/HIF-2alpha+ and 11 VHL-deficient/HIF-2alpha+ tumors were selected for array CGH.
2008-12-27 | E-GEOD-13282 | biostudies-arrayexpress
Project description:Investigation whether hypoxic stabilization of HIF-1alpha quantitatively or qualitatively modifies the gene expression pattern induced by poly I:C, a TLR ligand that does not induce normoxic HIF-1alpha stabilization on its own (non-HIF-1alpha-stabilizing TLR ligand). Keywords: Comparison of single and combined treatment
2011-06-29 | GSE24995 | GEO
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.
2013-09-05 | E-GEOD-44925 | biostudies-arrayexpress