Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNAi of human HUVEC cells knocked down for HDAC isoenzymes reveals sHDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells

ABSTRACT: Class IIa histone deacetylases (HDACs) are signal-responsive regulators of gene expression involved in vascular homeostasis. To investigate the differential role of class IIa HDACs for the regulation of angiogenesis, we used siRNA to specifically suppress the individual HDAC isoenzymes. Among the HDAC isoforms tested, silencing of HDAC5 exhibited a unique pro-angiogenic effect evidenced by increased endothelial cell migration, sprouting and tube formation. Consistently, overexpression of HDAC5 decreased sprout formation, indicating that HDAC5 is a negative regulator of angiogenesis. The anti-angiogenic activity of HDAC5 was independent of MEF2 binding and its deacetylase activity, but required a nuclear localization indicating that HDAC5 might affect the transcriptional regulation of gene expression. To identify putative HDAC5 targets, we performed microarray expression analysis. Silencing of HDAC5 increased the expression of fibroblast growth factor 2 (FGF2) and angiogenic guidance factors including Slit2. Antagonization of FGF2 or Slit2 reduced sprout induction in response to HDAC5 siRNA. ChIP assays demonstrate that HDAC5 binds to the promoter of FGF2 and Slit2. In summary, HDAC5 represses angiogenic genes, like FGF2 and Slit2, which causally contribute to capillary-like sprouting of endothelial cells. The de-repression of angiogenic genes by HDAC5 inactivation may provide a useful therapeutic target for induction of angiogenesis. Experiment Overall Design: 6 samples: 3x siSCRAMBLED transfected HUVEC (control) + 3x siHDAC5 transfected HUVEC 24h after transfection

ORGANISM(S): Homo sapiens

SUBMITTER: Carmen Urbich

PROVIDER: E-GEOD-15499 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells

Project description:Class IIa histone deacetylases (HDACs) are signal-responsive regulators of gene expression involved in vascular homeostasis. To investigate the differential role of class IIa HDACs for the regulation of angiogenesis, we used siRNA to specifically suppress the individual HDAC isoenzymes. Among the HDAC isoforms tested, silencing of HDAC5 exhibited a unique pro-angiogenic effect evidenced by increased endothelial cell migration, sprouting and tube formation. Consistently, overexpression of HDAC5 decreased sprout formation, indicating that HDAC5 is a negative regulator of angiogenesis. The anti-angiogenic activity of HDAC5 was independent of MEF2 binding and its deacetylase activity, but required a nuclear localization indicating that HDAC5 might affect the transcriptional regulation of gene expression. To identify putative HDAC5 targets, we performed microarray expression analysis. Silencing of HDAC5 increased the expression of fibroblast growth factor 2 (FGF2) and angiogenic guidance factors including Slit2. Antagonization of FGF2 or Slit2 reduced sprout induction in response to HDAC5 siRNA. ChIP assays demonstrate that HDAC5 binds to the promoter of FGF2 and Slit2. In summary, HDAC5 represses angiogenic genes, like FGF2 and Slit2, which causally contribute to capillary-like sprouting of endothelial cells. The de-repression of angiogenic genes by HDAC5 inactivation may provide a useful therapeutic target for induction of angiogenesis.

2009-04-02 | GSE15499 | GEO

Slit2 modifies VEGF-induced angiogenic responses in rabbit skeletal muscle by inducing capillary sprouting and decreasing vascular permeability via reduced eNOS activity

Project description:Rationale: Slit2 is a possible modulator of vascular endothelial growth factor (VEGF) - induced angiogenesis, but its effects have not been tested in large animal models. Objective: We studied the effect of Slit2 on therapeutic angiogenesis induced by VEGF receptor 2 (VEGFR2) ligands Vammin and VEGF-DΔNΔC in vivo in rabbit skeletal muscles. The Slit2 target genes were also studied by RNA sequencing (RNA-Seq) in endothelial cells. Methods and Results: Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Signaling experiments and gene expression analyses were performed to study mechanisms of Slit2 action. Slit2 decreased VEGFR2-mediated vascular permeability. It also reduced VEGFR2-mediated increase in blood perfusion and capillary enlargement, whereas sprouting of the capillaries was increased. Slit2 gene transfer alone did not have any effects on vascular functions or morphology. VEGFR2 activation was not affected by Slit2, but eNOS phosphorylation was diminished. The transcriptome profiling showed Slit2 downregulating angiogenesis-related genes such as nuclear receptor subfamily 4 group A member 1 (NR4A1) and Stanniocalcin-1 (STC-1) as well as genes related to endothelial cell migration and vascular permeability. Conclusions: Combining Slit2 with VEGFs adjusts VEGFR2-mediated angiogenic effects into a more physiological direction. This possibly allows the use of higher VEGF vector doses to achieve a more widespread vector and VEGF distribution in the target tissues leading to a better therapeutic outcome while reducing excess vascular permeability. HUVEC mRNA profiles after adenoviral vector gene transfers in duplicate.

2015-05-26 | E-GEOD-63283 | biostudies-arrayexpress

Slit2 modifies VEGF-induced angiogenic responses in rabbit skeletal muscle by inducing capillary sprouting and decreasing vascular permeability via reduced eNOS activity

2015-05-26 | GSE63283 | GEO

Transcriptome profiling of human urothelial carcinoma cell lines RT-112, VM-Cub-1, SW1710, UMUC3 and a benign urothelial control HBLAK engineered to stably express HDAC5 against their vector control

Project description:Aberrant expression of histone deacetylases (HDACs) and their activity are associated with a broad range of tumor development. However, based on cell or tissue types, class IIA HDACs such as HDAC4 and HDAC5 may facilitate or inhibit cancer progression. The goal of this project is to examine the gene expression changes caused by HDAC5 expression. Here, we studied the effects of stable expression of HDAC5 (that is normally downregulated or have a weak basal expression) in four urothelial carcinoma (UC) cell lines (RT112, VM-Cub-1, SW1710, and UM-UC-3) by rRNA-depleted RNA-sequencing in comparison to their vector controls. We observed that HDAC5 expression in VM-Cub-1 triggered a drastic phenotype change from an epitheloid to a mesenchymal (i.e., epithelial-mesenchymal transition, EMT) and altogether diminished cell proliferation of the other three cell lines. Our RNA-seq data are in line with the phenotypic transformation of VM-Cub-1. In addition, we also performed a gene expression profiling of HBLAK, a spontaneously immortalized from primary human bladder epithelial cells that can be directly compared with the four UC vector cells. HBLAK vector cells only were included for RNA-seq as the cells failed to express HDAC5 after lentiviral transduction and selection.

2019-11-13 | E-MTAB-8418 | biostudies-arrayexpress

Differential gene expression analysis of 4days post fertilization (dpf) wildtype and flt1ka601zebrafish mutants to identify venous sprouting associated genes

Project description:Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube. Upon loss of neuronal flt1, ectopic sprouts emanate from veins involving special angiogenic cell behaviors including nuclear positioning and a molecular signature distinct from primary artery or secondary venous sprouting. Manipulation of AV identity or Notch signaling established that ectopic sprouting in flt1 mutants requires venous endothelium. Conceptually our data suggest that spinal cord vascularization proceeds from veins involving two-tiered regulation of neuronal sFlt1 and Vegfaa via a novel sprouting mode.

2016-11-01 | GSE89350 | GEO

Protein expression profiling of human urothelial carcinoma cell lines RT-112, VM-Cub-1, SW1710, UMUC3 and a benign urothelial control HBLAK engineered to stably express HDAC5 against their vector control

Project description:Aberrant expression of histone deacetylases (HDACs) and their activity are associated with a broad range of tumor development. However, based on cell or tissue types, class IIA HDACs such as HDAC4 and HDAC5 may facilitate or inhibit cancer progression. The goal of this project is to examine the overall proteome changes caused by HDAC5 expression. Here, we studied the effects of stable expression of HDAC5 (that is normally downregulated or have a weak basal expression) in four urothelial carcinoma (UC) cell lines (RT112, VM-Cub-1, SW1710, and UM-UC-3) by mass spectrometry in comparison to their vector controls. We observed that HDAC5 expression in VM-Cub-1 triggered a drastic phenotype change from an epitheloid to a mesenchymal (i.e., epithelial-mesenchymal transition, EMT) and altogether diminished cell proliferation of the other three cell lines. Our mass-spec data are in line with the phenotypic transformation of VM-Cub-1. In addition, we also performed a protein expression profiling of HBLAK, a spontaneously immortalized from primary human bladder epithelial cells that can be directly compared with the four UC vector cells. HBLAK vector cells only were included for mass-spec as the cells failed to express HDAC5 after lentiviral transduction and selection.

2022-03-14 | PXD014448 | Pride

KSHV vIRF3 promotes angiogenesis of lymphatic endothelial cells (LECs)

Project description:Herein, we report viral interferon regulatory factor 3 (vIRF3) as a pro-angiogenic factor together with HDAC5 that coordinates with LEC transcriptome, thus resulting in hyper-sprouting formation and ultimately leading to abnormal lymphangiogenesis. Overexpression of vIRF3 in LECs but not blood endothelial cells (BECs) exhibited a unique KSHV-associated angiogenic effect, evidenced by elongated spindle shape, sprouting, and tube formation. Furthermore, using vIRF3 knockout recombinant KSHV, we confirmed that vIRF3 is a critical factor of KSHV-mediated lymphangiogenesis in primary LECs.

2017-12-19 | GSE102132 | GEO

Members of the microRNA-17-92 cluster exhibit a cell intrinsic anti-angiogenic function in endothelial cells

Project description:MicroRNAs are endogenously expressed small non-coding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a and -20a significantly inhibited 3D spheroid sprouting in vitro, whereas inhibition of miR-17, -18a and -20a augmented endothelial cell (EC) sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in matrigel plugs, whereas antagomirs, that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several pro-angiogenic genes. Specifically, Janus kinase 1 (Jak1) was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell intrinsic anti-angiogenic activity in ECs. Inhibition of miR-17/20 specifically augmented neovascularization of matrigel plugs, but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo. 6 samples of 3 independent experiments (n=3): per experiment Pre-miR-Co (10 nM, Ambion) and Pre-miR-17 (10 nM, Ambion) transfected HUVEC 24h after transfection

2010-03-23 | E-GEOD-20745 | biostudies-arrayexpress

Histone modifications regulated by HDAC5 in PDAC cells

Project description:HDAC5 belongs to Class IIa histone deacetylases and forms corepressor complex with HDAC3. To understand the epignetic regulations by HDAC5, we performed ChIP-seq analysis of H3K4me3, H3K27ac and H3K9ac in PDAC cells overexpressing GFP or HDAC5, and in HDAC5 escaper cells with HDAC5 knockdown or scramble control.

2020-04-27 | GSE149125 | GEO

HDAC5-ChIP seq data in HDAC5-driven KRASG12D-independent PDAC cells

Project description:HDAC5 belongs to Class IIa histone deacetylases and forms corepressor complex with HDAC3 to suppess gene expression. To identify the target genes of HDAC5, we performed ChIP-seq analysis in FLAG-tagged HDAC5 PDAC escaper cells. HDAC5 binding chromatins were pulled down by HDAC5 antibody and FLAG antibody as replicates.

2020-04-27 | GSE129549 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data