Faculty Opinions recommendation of YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation.

2017 ◽  
Author(s):  
Martin A Schwartz
Keyword(s):  
Sprouting Angiogenesis

Endothelial Tip Cell Invasive Behaviour During Sprouting Angiogenesis is Controlled by Myosin IIA-Dependent Inhibition of Arp2/3 Activity

2020 ◽  
Author(s):  
Ana M. Figueiredo ◽  
Pedro Barbacena ◽  
Rita Ferreira ◽  
Ana Russo ◽  
Silvia Vaccaro ◽  
...  
Keyword(s):  
Tip Cell ◽  
Sprouting Angiogenesis ◽  
Dependent Inhibition ◽  
Myosin Iia

scholarly journals Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David M. Favara ◽  
Ines Liebscher ◽  
Ali Jazayeri ◽  
Madhulika Nambiar ◽  
Helen Sheldon ◽  
...  
Keyword(s):  
Transcriptional Profiling ◽  
Gc Content ◽  
Luciferase Reporter ◽  
Cell Phenotype ◽  
Beta Catenin ◽  
Sprouting Angiogenesis ◽  
Proteolytic Site ◽  
Elevated Expression ◽  
Adhesion Gpcr

AbstractADGRL4/ELTD1 is an orphan adhesion GPCR (aGPCR) expressed in endothelial cells that regulates tumour angiogenesis. The majority of aGPCRs are orphan receptors. The Stachel Hypothesis proposes a mechanism for aGPCR activation, in which aGPCRs contain a tethered agonist (termed Stachel) C-terminal to the GPCR-proteolytic site (GPS) cleavage point which, when exposed, initiates canonical GPCR signalling. This has been shown in a growing number of aGPCRs. We tested this hypothesis on ADGRL4/ELTD1 by designing full length (FL) and C-terminal fragment (CTF) ADGRL4/ELTD1 constructs, and a range of potential Stachel peptides. Constructs were transfected into HEK293T cells and HTRF FRET, luciferase-reporter and Alphascreen GPCR signalling assays were performed. A stable ADGRL4/ELTD1 overexpressing HUVEC line was additionally generated and angiogenesis assays, signalling assays and transcriptional profiling were performed. ADGRL4/ELTD1 has the lowest GC content in the aGPCR family and codon optimisation significantly increased its expression. FL and CTF ADGRL4/ELTD1 constructs, as well as Stachel peptides, did not activate canonical GPCR signalling. Furthermore, stable overexpression of ADGRL4/ELTD1 in HUVECs induced sprouting angiogenesis, lowered in vitro anastomoses, and decreased proliferation, without activating canonical GPCR signalling or MAPK/ERK, PI3K/AKT, JNK, JAK/HIF-1α, beta catenin or STAT3 pathways. Overexpression upregulated ANTXR1, SLC39A6, HBB, CHRNA, ELMOD1, JAG1 and downregulated DLL4, KIT, CCL15, CYP26B1. ADGRL4/ELTD1 specifically regulates the endothelial tip-cell phenotype through yet undefined signalling pathways.

scholarly journals Lack of WWC2 Protein Leads to Aberrant Angiogenesis in Postnatal Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5321
Author(s):  
Viktoria Constanze Brücher ◽  
Charlotte Egbring ◽  
Tanja Plagemann ◽  
Pavel I. Nedvetsky ◽  
Verena Höffken ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Control Group ◽  
Knock Out ◽  
Ocular Angiogenesis ◽  
Sprouting Angiogenesis ◽  
Adult Mice ◽  
Upstream Regulator ◽  
Knock Out Mice ◽  
Hippo Signalling

The WWC protein family is an upstream regulator of the Hippo signalling pathway that is involved in many cellular processes. We examined the effect of an endothelium-specific WWC1 and/or WWC2 knock-out on ocular angiogenesis. Knock-outs were induced in C57BL/6 mice at the age of one day (P1) and evaluated at P6 (postnatal mice) or induced at the age of five weeks and evaluated at three months of age (adult mice). We analysed morphology of retinal vasculature in retinal flat mounts. In addition, in vivo imaging and functional testing by electroretinography were performed in adult mice. Adult WWC1/2 double knock-out mice differed neither functionally nor morphologically from the control group. In contrast, the retinas of the postnatal WWC knock-out mice showed a hyperproliferative phenotype with significantly enlarged areas of sprouting angiogenesis and a higher number of tip cells. The branching and end points in the peripheral plexus were significantly increased compared to the control group. The deletion of the WWC2 gene was decisive for these effects; while knocking out WWC1 showed no significant differences. The results hint strongly that WWC2 is an essential regulator of ocular angiogenesis in mice. As an activator of the Hippo signalling pathway, it prevents excessive proliferation during physiological angiogenesis. In adult animals, WWC proteins do not seem to be important for the maintenance of the mature vascular plexus.

scholarly journals Resistance Mechanisms of Anti-angiogenic Therapy and Exosomes-Mediated Revascularization in Cancer

2020 ◽  
Vol 8 ◽  
Author(s):  
Ye Zeng ◽  
Bingmei M. Fu
Keyword(s):  
Vasculogenic Mimicry ◽  
Resistance Mechanisms ◽  
Vascular Endothelial ◽  
Beneficial Effects ◽  
Sprouting Angiogenesis ◽  
Intussusceptive Angiogenesis ◽  
Angiogenic Therapy ◽  
Tumor Neovascularization ◽  
Endothelial Growth Factor

Anti-angiogenic therapies (AATs) have been widely used for cancer treatment. But the beneficial effects of AATs are short, because AAT-induced tumor revascularization facilitates the tumor relapse. In this mini-review, we described different forms of tumor neovascularization and revascularization including sprouting angiogenesis, vessel co-option, intussusceptive angiogenesis, and vasculogenic mimicry, all of which are closely mediated by vascular endothelial growth factor (VEGF), angiopoietins, matrix metalloproteinases, and exosomes. We also summarized the current findings for the resistance mechanisms of AATs including enhancement in pro-angiogenic cytokines, heterogeneity in tumor-associated endothelial cells (ECs), crosstalk between tumor cells and ECs, masking of extracellular vesicles, matrix stiffness and contributions from fibroblasts, macrophages and adipocytes in the tumor microenvironment. We highlighted the revascularization following AATs, particularly the role of exosome stimulating factors such as hypoxia and miRNA, and that of exosomal cargos such as cytokines, miRNAs, lncRNAs, and circRNAs from the tumor ECs in angiogenesis and revascularization. Finally, we proposed that renormalization of tumor ECs would be a more efficient cancer therapy than the current AATs.

scholarly journals Rudhira/BCAS3 couples microtubules and intermediate filaments to promote cell migration for angiogenic remodeling

2019 ◽  
Vol 30 (12) ◽  
pp. 1437-1450 ◽  
Author(s):  
Divyesh Joshi ◽  
Maneesha S. Inamdar
Keyword(s):  
Cell Migration ◽  
Intermediate Filaments ◽  
Cross Talk ◽  
Control Cell ◽  
The Novel ◽  
Mouse Development ◽  
Cytoskeleton Organization ◽  
Sprouting Angiogenesis ◽  
Promote Cell Migration ◽  
Necessary And Sufficient

Blood vessel formation requires endothelial cell (EC) migration that depends on dynamic remodeling of the cytoskeleton. Rudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein essential for EC migration and sprouting angiogenesis during mouse development and is implicated in metastatic disease. Here, we report that Rudhira mediates cytoskeleton organization and dynamics during EC migration. Rudhira binds to both microtubules (MTs) and vimentin intermediate filaments (IFs) and stabilizes MTs. Rudhira depletion impairs cytoskeletal cross-talk, MT stability, and hence focal adhesion disassembly. The BCAS3 domain of Rudhira is necessary and sufficient for MT-IF cross-linking and cell migration. Pharmacologically restoring MT stability rescues gross cytoskeleton organization and angiogenic sprouting in Rudhira-depleted cells. Our study identifies the novel and essential role of Rudhira in cytoskeletal cross-talk and assigns function to the conserved BCAS3 domain. Targeting Rudhira could allow tissue-restricted cytoskeleton modulation to control cell migration and angiogenesis in development and disease.

scholarly journals Endothelial Cell mTOR Complex-2 Regulates Sprouting Angiogenesis

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135245 ◽  
Author(s):  
Maikel A. Farhan ◽  
Katia Carmine-Simmen ◽  
John D. Lewis ◽  
Ronald B. Moore ◽  
Allan G. Murray
Keyword(s):  
Endothelial Cell ◽  
Sprouting Angiogenesis
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