This SuperSeries is composed of the SubSeries listed below.
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Age, Specimen part, Cell line, Treatment
View SamplesRegulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Specimen part, Cell line, Treatment
View SamplesRegulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Specimen part, Cell line
View SamplesEstrogen receptor (ER) is a key regulator of breast growth and breast cancer development. However, the role of ER in metabolic reprogramming, a hallmark of cancer, is not well documented. In this study, using an integrated approach combining genome-wide mapping of chromatin bound ER with estrogen induced transcript and metabolic profiling, we demonstrate that ER reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline metabolism. We show, for the first time, that the ER target gene choline phosphotransferase 1 (CHPT1) plays an essential role in estrogen induced increases in phosphatidylcholine (PtdCho) levels and that CHPT1 promotes tumorigenesis and proliferation. Furthermore, we show that CHPT1 is overexpressed in tumors compared to normal breast. We also demonstrate that ER promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ER for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ER target CHPT1 in breast cancer supports its potential as a therapeutic target.
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Treatment
View SamplesThe contribution of aberrant DNA methylation and the downstream effects in tumorogenesis through silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations can be reversed, we investigated the effects of the epigenetic therapy in breast cancer cell lines.
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Treatment
View SamplesThis experiment tests the hypothesis that interleukin-1 promotes SMC phenotypic modulation to a distinct inflammatory state relative to the growth factor PDGF-DD.
Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.
No sample metadata fields
View SamplesGene expression profiling of several wildtype strains of zebrafish embryos. The samples were pooled from several developmental stages ranging from 2 to 7 days post fertilization. This breadth of sampling gives a broad idea of genes expressed during early development and SNPs associated with wildtype strains.
RNA-seq-based mapping and candidate identification of mutations from forward genetic screens.
No sample metadata fields
View SamplesMinocycline is a potent modulator of retinal microglia Overall design: Global mRNA expression analysis of CD1 mouse retinas in control, light damage and light damage plus minocycline conditions
Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration.
No sample metadata fields
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