GEO accession GSE210502 is currently private and is scheduled to be released on Oct 01, 2025.
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ABSTRACT:
PROVIDER: PRJNA865806 | ENA |
REPOSITORIES: ENA
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Project description:We generated recombinant human sVE-cadherin (extracellular domains EC1-5) which was applied to human dermal microvascular endothelial cells (HDMEC) to investigate it`s role in endothelial barrier function. In other experiments we observed that sVE-cadherin disrupted endothelial barrier function by dismantling the VE-cadherin complex at cell borders via VE-PTP-dependent RhoA activation. The sequencing project compares untreated HDMEC vs treated cells.
2025-10-01 | GSE210502 | GEO
Project description:Rationale: The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumours, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular inter-endothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, vascular endothelial (VE)-cadherin (VEC), upregulate genes with key roles in endothelial differentiation and stability. Objective: We aim at understanding the molecular mechanisms through which VEC triggers the expression of a set of genes involved in endothelial differentiation and vascular stabilization. Methods and Results: We compared a VEC-null cell line with the same line reconstituted with VEC wild type cDNA. VEC expression and clustering upregulated endothelial-specific genes with key roles in vascular stabilization including claudin-5, Vascular Endothelial-Protein Tyrosine Phosphatase (VE-PTP) and von Willebrand factor (vWf). Mechanistically VEC exerts this effect by inhibiting Polycomb protein activity on the specific gene promoters. This is achieved by preventing nuclear translocation of FoxO1 and β-catenin, which contribute to Polycomb repressive complex-2 (PRC2) binding to promoter regions of claudin-5, VE-PTP and vWf. VE-cadherin/β-catenin complex also sequesters a core subunit of PRC2 (Ezh2) at the cell membrane, preventing its nuclear translocation. Inhibition of Ezh2/VE-cadherin association increases Ezh2 recruitment to claudin-5, VE-PTP and vWf promoters, causing gene downregulation. RNAseq comparison of VEC-null and VEC-positive cells suggested a more general role of VE-cadherin in activating endothelial genes and triggering a vascular stability-related gene expression program. In pathological angiogenesis of human ovarian carcinomas, reduced VEC expression paralleled decreased levels of Claudin-5 and VE-PTP. Conclusions: These data extend the knowledge of Polycomb-mediated regulation of gene expression to endothelial cell differentiation and vessel maturation. The identified mechanism opens novel therapeutic opportunities to modulate endothelial gene expression and induce vascular normalization through pharmacological inhibition of the Polycomb-mediated repression system. Keywords: Polycomb, endothelial cells, VE-cadherin, vessel maturation, vascular biology, vascular permeability, cell signalling, epigenetics, gene regulation. Downloaded from http://circres.ahajour Conclusions: These data extend the knowledge of Polycomb-mediated regulation of gene expression to endothelial cell differentiation and vessel maturation. The identified mechanism opens novel therapeutic opportunities to modulate endothelial gene expression and induce vascular normalization through pharmacological inhibition of the Polycomb-mediated repression system
2019-10-19 | GSE139092 | GEO
Project description:The aim of the experiment was to compare a newly defined population VE-Cadherin+GFP+ to control populations, VE-Cadherin- GFP+ and VE-Cadherin+GFP-.
2019-04-20 | GSE113403 | GEO
Project description:Inhibition of VE-PTP, an endothelial receptor type tyrosine phosphatase, triggers phosphorylation of the tyrosine kinase receptor Tie-2, which leads to the suppression of inflammation-induced vascular permeability. Analyzing the underlying mechanism, we show here that inhibition of VE-PTP and activation of Tie-2 induce tyrosine phosphorylation of FGD5, a GTPase exchange factor (GEF) for Cdc42, and stimulate translocation of this GEF to cell contacts. Interfering with the expression of FGD5 blocked the junction stabilizing effect of VE-PTP inhibition in vitro and in vivo. Likewise, FGD5 was required for strengthening of cortical actin bundles and inhibiting radial stress fiber formation, which were each stimulated by VE-PTP inhibition. We identified Y820 of FGD5 as the direct substrate for VE-PTP. Inhibition of VE-PTP could no longer stabilize endothelial junctions or activate Cdc42 if endothelial cells expressed a Y820F point mutated version of FGD5. In contrast, FGD5-Y820F was still recruited to endothelial cell contacts. Thus, activation of FGD5 is a two-step process that comprises membrane recruitment and phosphorylation of Y820. These steps are necessary for the junction stabilizing effect that is stimulated by VE-PTP inhibition and Tie-2 activation.
2019-05-04 | PXD010959 | Pride
Project description:In order to identify genes regulated by VE-cadherin expression, we compared a mouse VE-cadherin null cell line (VEC null) with the same line reconstituted with VE-cadherin wild type cDNA (VEC positive). The morphological and functional properties of these cell lines were described previously [Lampugnani,M.G. et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J. Cell Biol. 161, 793-804 (2003)]. By Affymetrix gene expression analysis we found several genes up-regulated by VE-cadherin, among which claudin-5 reached remarkably high levels. The up-regulation of these genes required not only VE-cadherin expression but also cell confluence suggesting that VE-cadherin clustering at junctions was needed.
2008-07-06 | GSE11674 | GEO
Project description:Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of vascular permeability. Since VE-cadherin is also strongly expressed in placental trophoblasts, it is a prime candidate for a molecular mechanism of vascular mimicry by those cells. Here, we show that the VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua. VE-cadherin deficiency results in loss of spiral artery remodeling due to a lack of invasive trophoblasts, leading to decreased flow of maternal blood into the placenta, fetal growth retardation and death. Loss of trophoblast invasion prevents decidualization, extracellular matrix remodeling, and immune cell clearance. These studies identify VE-cadherin as essential for trophoblast migration and coordination of decidual changes during endovascular invasion. They further suggest endothelial proteins such as VE-cadherin that are expressed by trophoblasts may play functionally distinct roles that do not simply mimic those in ECs.
2021-11-30 | GSE189408 | GEO
Project description:The shear stress-regulated lncRNA LASSIE interacts with junctional proteins (e.g. PECAM-1, which interacts with VE-cadherin) and influences endothelial barrier function. Here we characterize the remodeling of the VE-Cadherin complex by the lncRNA LASSIE. LASSIE silenced HUVECs were subjected to co-immunoprecipitation using an anti-VE-cadherin antibody. Differentially associated proteins were identified by Mass spectrometry. This analysis revealed a significantly decreased association of cytoskeleton-linked proteins with VE-cadherin after silencing of LASSIE. Functional assays confirmed this result and characterized LASSIE as a stabilizer of junctional complexes in endothelial cells, important for normal shear stress sensing and barrier function.
2021-09-09 | PXD018725 | Pride
Project description:Bulk RNA sequencing of VE-Cadherin+GFP+, VE-Cadherin- GFP+ and VE-Cadherin+GFP- populations from E11.5 miR144/451+/GFP mouse yolk sac.
| PRJNA451028 | ENA
Project description:Endothelial cells (ECs) express two members of the cadherin family, VE- and N-cadherin. While VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE- or N-cadherin leads to early foetal lethality suggesting that these cadherins play a non-redundant role in vascular development. Goal of this study was to further investigate this hypothesis analyzing both additive and divergent functions of the two cadherins in ECs.
2012-01-10 | GSE34948 | GEO
Project description:Purpose: The goals of this study are to confirm whether CD5-2 works through VE-cadherin Methods: mRNA profiles of HUVEC and VE-cadherin-/- EC treated with either control or CD5-2 were generated by deep sequencing using Illumina Hiseq4000 platform and 150 bp paired-end reads were generated. Reference genome and gene model annotation files were downloaded from genome website browser (NCBI/UCSC/Ensembl) directly. Indices of the reference genome were built using Bowtie (v2.2.3) and paired-end clean reads were aligned to the reference genome using TopHat (v2.0.12). Differentially expressed genes were then determined using DESeq R package (v1.12.0). The resulting P-values were adjusted using the Benjamini and Hochberg’s approach for controlling the False Discovery Rate (FDR). Genes with an adjusted P-value<0.05 and FDR<0.005 were assigned as differentially expressed. Results: 585 differentially expressed genes (DEGs) in CD5-2 treated ECs compared with control treated ECs (P < 0.05; false discovery rate [FDR] ≤ 0.005). In stark contrast to that seen in normal ECs, in VE-cadherin-/- ECs, no gene was significantly differently expressed between control and CD5-2 treated group when using the same cut-off criteria, Conclusions: Our study suggests VE-cadherin is essential for the CD5-2 mediated gene changes
2020-05-07 | GSE149948 | GEO