Endothelial TIE1 restricts angiogenic sprouting to coordinate vein assembly in synergy with its homologue TIE2
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE229118 | GEO | 2023/06/23
REPOSITORIES: GEO
Similar Datasets
Project description:Endothelial TIE1 restricts angiogenic sprouting to coordinate vein assembly in synergy with its homologue TIE2
| PRJNA952988 | ENA
Project description:TIE1 regulates leaf development by repressing leaf differentiation because the semi-dominant mutant tie1-D by activation tagging displays small and hyponastic leaves and the differentiation of leaf epidermal cells is delayed in the tie1-D mutant, whereas disruption of TIE1 causes epinastic leaves with early differentiated epidermal cells. We used microarrays to investigate the molecular base underpinning the phenotypes of TIE1-overexpressing plants. Aerial parts of 14-day-old seedlings from wild-type and GFP-TIE1-15 were collected for RNA extraction and hybridization on Affymetrix microarrays.
2012-05-26 | E-GEOD-38282 | biostudies-arrayexpress
Project description:The endothelial cell (EC)-specific receptor tyrosine kinases Tie1 and Tie2 are necessary for the remodeling and maturation of blood and lymphatic vessels. Angiopoietin-1 (Ang1) growth factor is a Tie2 agonist, whereas Ang2 functions as a context-dependent agonist/antagonist. The orphan receptor Tie1 modulates Tie2 activation, which is induced by association of angiopoietins with Tie2 in cis and across EC-EC junctions in trans Except for the binding of the C-terminal angiopoietin domains to the Tie2 ligand-binding domain, the mechanisms for Tie2 activation are poorly understood. We report here the structural basis of Ang1-induced Tie2 dimerization in cis and provide mechanistic insights on Ang2 antagonism, Tie1/Tie2 heterodimerization, and Tie2 clustering. We find that Ang1-induced Tie2 dimerization and activation occurs via the formation of an intermolecular β-sheet between the membrane-proximal (third) Fibronectin type III domains (Fn3) of Tie2. The structures of Tie2 and Tie1 Fn3 domains are similar and compatible with Tie2/Tie1 heterodimerization by the same mechanism. Mutagenesis of the key interaction residues of Tie2 and Tie1 Fn3 domains decreased Ang1-induced Tie2 phosphorylation and increased the basal phosphorylation of Tie1, respectively. Furthermore, the Tie2 structures revealed additional interactions between the Fn 2 (Fn2) domains that coincide with a mutation of Tie2 in primary congenital glaucoma that leads to defective Tie2 clustering and junctional localization. Mutagenesis of the Fn2-Fn2 interface increased the basal phosphorylation of Tie2, suggesting that the Fn2 interactions are essential in preformed Tie2 oligomerization. The interactions of the membrane-proximal domains could provide new targets for modulation of Tie receptor activity.
| S-EPMC5410806 | biostudies-literature
Project description:To investigate what kind of gene expression is regulated downstream of Tie1 signaling, we performed RNA-seq analyses on venous and lymphatic endothelial cells (ECs) between homozygous tie1 mutant embryos and their wild-type and heterozygous siblings during secondary sprouting, respectively. Our analyses indicate that Tie1 signaling controls a series of gene expression involved in lymphatic development including EC migration, proliferation, and differentiation.
2024-05-16 | GSE240329 | GEO
Project description:TIE1 regulates leaf development by repressing leaf differentiation because the semi-dominant mutant tie1-D by activation tagging displays small and hyponastic leaves and the differentiation of leaf epidermal cells is delayed in the tie1-D mutant, whereas disruption of TIE1 causes epinastic leaves with early differentiated epidermal cells. We used microarrays to investigate the molecular base underpinning the phenotypes of TIE1-overexpressing plants.
2012-05-27 | GSE38282 | GEO
Project description:The Tie family of endothelial-specific receptor tyrosine kinases is essential for cell proliferation, migration, and survival during angiogenesis. Despite considerable similarity, experiments with Tie1- or Tie2-deficient mice highlight distinct functions for these receptors in vivo. The Tie2 receptor is further unique with respect to its structurally homologous ligands. Angiopoietin-2 and -3 can function as agonists or antagonists; angiopoietin-1 and -4 are constitutive agonists. To address the role of Tie1 in angiopoietin-mediated Tie2 signaling and determine the basis for the behavior of the individual angiopoietins, we used an in vivo FRET-based proximity assay to monitor Tie1 and -2 localization and association. We provide evidence for Tie1-Tie2 complex formation on the cell surface and identify molecular surface areas essential for receptor-receptor recognition. We further demonstrate that the Tie1-Tie2 interactions are dynamic, inhibitory, and differentially modulated by angiopoietin-1 and -2. Based on the available data, we propose a unified model for angiopoietin-induced Tie2 signaling.
| S-EPMC2841065 | biostudies-literature
Project description:Purpose: identifying, with RNA-seq, genes targets of Tie1 during the cardiac development in zebrafish. Results: we identified several differential expressed genes, with an enrichment in ECM modulator genes.
2020-09-22 | GSE148957 | GEO
Project description:Angiogenic sprouting can contribute adaptively, or mal-adaptively, to a myriad of conditions including ischemic heart disease and cancer. While the cellular and molecular systems that regulate tip versus stalk endothelial cell (EC) specification during angiogenesis are known, those systems that regulate their distinct actions remain poorly understood. Pre-clinical and clinical findings support sustained adrenergic signaling in promoting angiogenesis, but links between adrenergic signaling and angiogenesis are lacking; importantly, adrenergic agents alter the activation status of the cAMP signaling system. Here, we show that the cAMP effector, PKA, acts in a cell autonomous fashion to constitutively reduce the in vitro and ex vivo angiogenic sprouting capacity of ECs. At a cellular level, we observed that silencing or inhibiting PKA in human ECs increased their invasive capacity, their generation of podosome rosettes and, consequently, their ability to degrade a collagen matrix. While inhibition of either Src-family kinases or of cdc42 reduced these events in control ECs, only cdc42 inhibition, or silencing, significantly impacted them in PKA(Cα)-silenced ECs. Consistent with these findings, cell-based measurements of cdc42 activity revealed that PKA activation inhibits EC cdc42 activity, at least in part, by promoting its interaction with the inhibitory regulator, guanine nucleotide dissociation inhibitor-α (RhoGDIα).
| S-EPMC6382826 | biostudies-literature
Project description:The ang1-Tie2 pathway is required for normal vascular development, but its molecular effectors are not well-defined during cardiac ontogeny. Here we show that endocardial specific attenuation of Tie2 results in mid-gestation lethality due to heart defects associated with a hyperplastic but simplified trabecular meshwork (fewer but thicker trabeculae). Reduced proliferation and production of endocardial cells (ECs) following endocardial loss of Tie2 results in decreased endocardial sprouting required for trabecular assembly and extension. The hyperplastic trabeculae result from enhanced proliferation of trabecular cardiomyocyte (CMs), which is associated with upregulation of Bmp10, increased retinoic acid (RA) signaling, and Erk1/2 hyperphosphorylation in the myocardium. Intriguingly, myocardial phenotypes in Tie2-cko hearts could be partially rescued by inhibiting in utero RA signaling with pan-retinoic acid receptor antagonist BMS493. These findings reveal two complimentary functions of endocardial Tie2 during ventricular chamber formation: ensuring normal trabeculation by supporting EC proliferation and sprouting, and preventing hypertrabeculation via suppression of RA signaling in trabecular CMs.
| S-EPMC6629240 | biostudies-literature
Project description:BackgroundMaintaining the stability and maturation of blood vessels is of paramount importance for the vessels to carry out their physiological function. Smooth muscle cells (SMCs), pericytes, and mesenchymal stem cells (MSCs) are involved in the maturation process of the newly formed vessels. The aim of this study was to investigate whether transforming growth factor beta 1 (TGF-β1) treatment could enhance pericyte-like properties of dental pulp stem cells (DPSCs) and how TGF-β1-treated DPSCs for 7 days (T-DPSCs) stabilize the newly formed blood vessels.MethodsWe utilized TGF-β1 to treat DPSCs for 1, 3, 5, and 7 days. Western blotting and immunofluorescence were used to analyze the expression of SMC markers. Functional contraction assay was conducted to assess the contractility of T-DPSCs. The effects of T-DPSC-conditioned media (T-DPSC-CM) on human umbilical vein endothelial cell (HUVEC) proliferation and migration were examined by MTT, wound healing, and trans-well migration assay. Most importantly, in vitro 3D co-culture spheroidal sprouting assay was used to investigate the regulating role of vascular endothelial growth factor (VEGF)-angiopoietin (Ang)-Tie2 signaling on angiogenic sprouting in 3D co-cultured spheroids of HUVECs and T-DPSCs. Angiopoietin 2 (Ang2) and VEGF were used to treat the co-cultured spheroids to explore their roles in angiogenic sprouting. Inhibitors for Tie2 and VEGFR2 were used to block Ang1/Tie2 and VFGF/VEGFR2 signaling.ResultsWestern blotting and immunofluorescence showed that the expression of SMC-specific markers (α-SMA and SM22α) were significantly increased after treatment with TGF-β1. Contractility of T-DPSCs was greater compared with that of DPSCs. T-DPSC-CM inhibited HUVEC migration. In vitro sprouting assay demonstrated that T-DPSCs enclosed HUVECs, resembling pericyte-like cells. Compared to co-culture with DPSCs, a smaller number of HUVEC sprouting was observed when co-cultured with T-DPSCs. VEGF and Ang2 co-stimulation significantly enhanced sprouting in HUVEC and T-DPSC co-culture spheroids, whereas VEGF or Ang2 alone exerted insignificant effects on HUVEC sprouting. Blocking Tie2 signaling reversed the sprouting inhibition by T-DPSCs, while blocking VEGF receptor (VEGFR) signaling boosted the sprouting inhibition by T-DPSCs.ConclusionsThis study revealed that TGF-β1 can induce DPSC differentiation into functional pericyte-like cells. T-DPSCs maintain vessel stability through Ang1/Tie2 and VEGF/VEGFR2 signaling.
| S-EPMC8112067 | biostudies-literature