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

The downstream molecules of Notch signaling in vascular endothelial cell senescence

ABSTRACT: To further investigate the mechanism how the decline in Notch signaling induces premature senescence in endothelial cells, we performed microarray analysis and identified Id1 nd DUSP1 as the downstream molecules of Notch pathway. In quantitative PCR and western blot analyses, the expression level of Id1 and DUSP1 increased in Notch1 over-expressing endothelial cells and decreased in knockdown similar to the result of microarray. The gene expression of human unbilical endothelial vein cells (HUVEC) infected with retroviral vectors encoding Jagged1, Jagged1-shRNA, or Notch1-shRNA. HUVEC infected with empty vector was used as a control. In each genotypes, three independent lines at passage 8 were performed.

ORGANISM(S): Homo sapiens

SUBMITTER: Yohko Yoshida

PROVIDER: E-GEOD-40403 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

The downstream molecules of Notch signaling in vascular endothelial cell senescence

Project description:To further investigate the mechanism how the decline in Notch signaling induces premature senescence in endothelial cells, we performed microarray analysis and identified Id1 nd DUSP1 as the downstream molecules of Notch pathway. In quantitative PCR and western blot analyses, the expression level of Id1 and DUSP1 increased in Notch1 over-expressing endothelial cells and decreased in knockdown similar to the result of microarray.

2012-08-28 | GSE40403 | GEO

Notch-Jagged signaling complex defined by an interaction mosaic

Project description:The Notch signaling system links cellular fate to that of its neighbors, driving proliferation, apoptosis, and cell differentiation in metazoan organisms, whereas dysfunction leads to debilitating developmental disorders and cancers. Here we probe the molecular architecture of mammalian Notch1 full ectodomain in complex with the canonical ligand Jagged1 using cross-linking mass spectrometry (XL-MS). Our data reveals that three Jagged1 sites, C2-epidermal growth factor (EGF) 1, EGF10 and cysteine-rich domain (CRD), are in proximity to the Notch1 negative regulatory region (NRR) in the Notch1-Jagged1 full ectodomain complex. We verified direct interactions and identified additional interacting regions by quantitative-binding experiments. In addition, XL-MS and structural analysis reveal Notch1 and Jagged1 ectodomain intramolecular interactions and structural flexibility that support the formation of backfolded architectures. Together the data suggest a direct and intricate role for the different extracellular regions of Notch1 and Jagged1 in the activation and regulation of Notch1 signaling.

2021-07-08 | PXD023072 | Pride

Deubiquitinase USP10 regulates Notch signaling in the endothelium

Project description:Notch signaling is critical for vascular morphogenesis by co-determining the sprouting behavior of endothelial cells. Here, we investigate the function of ubiquitin-specific peptidase 10 (USP10) in regulation of the turnover of the NOTCH1 intracellular domain. HUVEC were transfected with scrambled or USP10 targeting siRNA and then stimulated by treatment with DLL4 or control. RNA for analysis was isolated after 24 hours of DLL4 stimulation.

2019-04-26 | E-MTAB-7774 | biostudies-arrayexpress

Inhibition of endothelial Notch signaling attenuates inflammation [ChIP-Seq]

Project description:Vascular endothelial cells upregulate the Notch ligand Jagged1 in response to inflammatory activation. Here we show that abrogation of endothelial Notch1 signaling impairs induction of key inflammatory target genes. Accordingly, inducible endothelial-targeted knockout of the canonical Notch transcription factor RBPJ reduces inflammation in a murine model of contact hypersensitivity, while overexpression of constitutive active Notch1 has the opposite effect. We show that the proinflammatory role of Notch1 can be attributed to direct genomic priming of the inflammatory landscape involving crosstalk with NF-κB/RelA and selective activation of enhancers associated with Notch-dependent inflammatory genes. This is the first evidence that canonical Notch signaling supports endothelial activation in response to inflammatory cytokines on the chromatin level.

2018-08-29 | GSE87552 | GEO

Expression profiling after ICAP1 or constitutive active NOTCH1 over expression in human umbilical vein endothelial cells

Project description:ICAP1 (also known as ITG1BP1) is a protein interaction partner of beta1-integrins and the cerebral cavernous malformation protein 1 (CCM1, also known as KRIT1). In mice Icap1 plays an important role for bone development. The function of ICAP1 in endothelial cells is poorly understood. However, the interactions with beta1-integrins and CCM1 suggest that ICAP1 should play an important role also in endothelial cells. We obtained data that ICAP1 might activate the Delta-Notch signaling cascade, a critical regulator of endothelial proliferation, migration and sprouting angiogenesis. This genome-wide expression analysis is aimed to unravelling novel mechanisms or signaling pathways how ICAP1 functions in endothelial cells. Secondly, this study aimed at defining novel target genes of Notch signaling and finally to compare the gene expression patterns of ICAP1 and NOTCH1. We used human umbilical vein endothelial cells (HUVEC) as a model system to study ICAP1 and NOTCH1 functions after adenoviral over expression in comparison to GFP over expression as control. The results of this experiment suggest that ICAP1 and NOTCH1 control a series of genes involved in cell proliferation, migration and angiogenesis. A high proportion of ICAP1-regulated genes is also regulated by NOTCH1 in a very similar manner. Human umbilical vein endothelial cells were transduced with adenovirus expressing ICAP1, NOTCH1 (only the constitutive active intracellular domain) or GFP as control. 36 hours after transduction total RNA was isolated from duplicates for genome-wide expression analysis biological replicate: GFP_1, GFP_2 biological replicate: NOTCH1_1, NOTCH1_2 biological replicate: ICAP1_1, ICAP1_2

2010-07-30 | E-GEOD-18035 | biostudies-arrayexpress

Notch1 dose modulates endothelial gene expression

Project description:Purpose: To use RNA-Seq analysis of endothelial cell in various Notch1 alllels in order to determine transcrptional differencesas a consequence of Notch dose. Methods: Using a FACS sorting we generated high-throughput RNA-SEQ data of endothelials in various Notch1 alleles during development Results: Notch1 dose can alter gene expression in a subset of endothelial genes RNA-Seq was performed on endothelial cells isolated at e9.5 from embryos with various Notch1 alleles including N1+/+, N1+/-, N1+/vg, N112/vg, N112/-

2015-08-04 | E-GEOD-69276 | biostudies-arrayexpress

HEK NICD AP-MS - Notch signaling is a core patterning module for vascular morphogenesis, which co-determines the sprouting behaviour of endothelial cells (ECs)

Project description:Notch signaling is a core patterning module for vascular morphogenesis, which co-determines the sprouting behaviour of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability, and diminished Notch-induced target gene expression in ECs. In mice, loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase, which fine-tunes endothelial Notch responses during angiogenic sprouting.

2019-04-11 | PXD013192 | Pride

Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins

Project description:Vascular morphogenesis requires a delicate gradient of Notch signaling that is controlled, at least in part, by the distribution of ligands (Dll4 and Jagged1). How jagged1 (JAG1) expression is compartmentalized in the vascular plexus remains unclear. Here we showed that Jag1 mRNA is a direct target of zinc finger protein 36 (ZFP36), an RNA-binding protein involved in mRNA decay that we found robustly induced by VEGF. Endothelial cells lacking ZFP36 displayed high levels of JAG1 and increased angiogenic sprouting in vitro. Similarly, mice lackingZfp36in endothelial cells display mispatterned and increased levels of JAG1 in the developing retinal vascular plexus. Abnormal levels of JAG1 at the sprouting front altered NOTCH1 signaling, increasing the number of tip cells; a phenotype that was rescued by imposing haploinsufficiency ofJag1. Our findings reveal an important feedforward loop, whereby VEGF stimulates ZFP36, consequently suppressing Jag1 to enable adequate levels of Notch signaling during sprouting angiogenesis.

2023-12-04 | GSE235462 | GEO

Comparison of gene expression between Human umbilical vein endothelial cells and Human liver sinusoidal endothelial cells

Project description:To identify leukocyte adhesion receptors which differentially regulate recruitment in human liver sinusoidal endothelial cells compared to a protoptypic venular endothelium Gene expression was measured in four groups Group 1: cultured human liver sinusoidal endothelial cells (HSEC) Group 2: cultured human umbilical vein endothelial cells (HUVEC) Group3: Interferon gamma and tumour necrosisfactor alpha treated HSEC and Group 4: Interferon gamma and tumour necrosisfactor alpha treated HUVEC. Two replicates were used for each group.

2016-10-24 | E-GEOD-78020 | biostudies-arrayexpress

Endothelial Jag1-RBPJK signaling promotes inflammatory leukocyte recruitment and atherosclerosis

Project description:Aim: To determine the role of NOTCH during the response-to-injury and subsequent chronic inflammatory process of the arterial wall underlying atherosclerosis. Methods and results: We have generated an endothelial-specific RBPJK depleted mice using the Cdh5 cadherin promoter (ApoE-/-;RBPJflox/flox;Cdh5- CreERT). Endothelial-specific deletion of the Notch effector RBPJK or systemic deletion of the Notch1 receptor in athero-susceptible ApoE-/- mice fed a HC diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus. Intravital microscopy revealed decreased leukocyte rolling on the endothelium of ApoE-/-;RBPJflox/flox;Cdh5- CreERT, that correlated with the lesser presence of leukocyts and macrophages in the vascular wall. Consistent with this, transcriptome analysis revealed that proinflammatory and endothelial activation pathways were downregulated in atherosclerotic tissue of RBPJk-mutant mice.. Jagged1 signaling upregulation in endothelial cells promotes the physical interaction and nuclear translocation of the intracellular domain of the Notch1 receptor (N1ICD) with NF-kB,. This N1ICD and NF-kB interaction is required for reciprocal transactivation of target genes including vascular cell adhesion molecule-1 (Vcam1). Conclusions: Notch signaling pathway inactivation decreases leukocyte rolling, thereby preventing endothelial dysfunction and vascular inflammation. Thus attenuating Notch signaling may constitute a useful therapeutic strategy for atherosclerosis. Key words: atherosclerosis, endothelium, signaling pathways, Notch, NF-kB, transcriptional regulation

2017-06-30 | GSE69376 | 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