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https://www.readbyqxmd.com/read/28714969/endothelial-notch-signalling-limits-angiogenesis-via-control-of-artery-formation
#1
Sana S Hasan, Roman Tsaryk, Martin Lange, Laura Wisniewski, John C Moore, Nathan D Lawson, Karolina Wojciechowska, Hans Schnittler, Arndt F Siekmann
Angiogenic sprouting needs to be tightly controlled. It has been suggested that the Notch ligand dll4 expressed in leading tip cells restricts angiogenesis by activating Notch signalling in trailing stalk cells. Here, we show using live imaging in zebrafish that activation of Notch signalling is rather required in tip cells. Notch activation initially triggers expression of the chemokine receptor cxcr4a. This allows for proper tip cell migration and connection to the pre-existing arterial circulation, ultimately establishing functional arterial-venous blood flow patterns...
July 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28714968/dll4-and-notch-signalling-couples-sprouting-angiogenesis-and-artery-formation
#2
Mara E Pitulescu, Inga Schmidt, Benedetto Daniele Giaimo, Tobiah Antoine, Frank Berkenfeld, Francesca Ferrante, Hongryeol Park, Manuel Ehling, Daniel Biljes, Susana F Rocha, Urs H Langen, Martin Stehling, Takashi Nagasawa, Napoleone Ferrara, Tilman Borggrefe, Ralf H Adams
Endothelial sprouting and proliferation are tightly coordinated processes mediating the formation of new blood vessels during physiological and pathological angiogenesis. Endothelial tip cells lead sprouts and are thought to suppress tip-like behaviour in adjacent stalk endothelial cells by activating Notch. Here, we show with genetic experiments in postnatal mice that the level of active Notch signalling is more important than the direct Dll4-mediated cell-cell communication between endothelial cells. We identify endothelial expression of VEGF-A and of the chemokine receptor CXCR4 as key processes controlling Notch-dependent vessel growth...
July 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28711779/hyperactive-foxo1-results-in-lack-of-tip-stalk-identity-and-deficient-microvascular-regeneration-during-kidney-injury
#3
Lan T H Dang, Takahide Aburatani, Graham A Marsh, Bryce G Johnson, Stella Alimperti, Christine J Yoon, Angela Huang, Suzanne Szak, Naoki Nakagawa, Ivan Gomez, Shuyu Ren, Sarah K Read, Chris Sparages, Alfred C Aplin, Roberto F Nicosia, Chris Chen, Giovanni Ligresti, Jeremy S Duffield
Loss of the microvascular (MV) network results in tissue ischemia, loss of tissue function, and is a hallmark of chronic diseases. The incorporation of a functional vascular network with that of the host remains a challenge to utilizing engineered tissues in clinically relevant therapies. We showed that vascular-bed-specific endothelial cells (ECs) exhibit differing angiogenic capacities, with kidney microvascular endothelial cells (MVECs) being the most deficient, and sought to explore the underlying mechanism...
July 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28695891/the-endothelial-transcription-factor-erg-mediates-angiopoietin-1-dependent-control-of-notch-signalling-and-vascular-stability
#4
A V Shah, G M Birdsey, C Peghaire, M E Pitulescu, N P Dufton, Y Yang, I Weinberg, L Osuna Almagro, L Payne, J C Mason, H Gerhardt, R H Adams, A M Randi
Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation and stability. Here we identify the transcription factor ERG as a key regulator of endothelial Notch signalling. We show that ERG controls the balance between Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo, this regulation occurs selectively in the maturing plexus of the mouse developing retina, where Ang1/Tie2 signalling is active. We find that ERG mediates Ang1-dependent regulation of Notch ligands and is required for the stabilizing effects of Ang1 in vivo...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28656980/neurovascular-egfl7-regulates-adult-neurogenesis-in-the-subventricular-zone-and-thereby-affects-olfactory-perception
#5
Frank Bicker, Verica Vasic, Guilherme Horta, Felipe Ortega, Hendrik Nolte, Atria Kavyanifar, Stefanie Keller, Nevenka Dudvarski Stankovic, Patrick N Harter, Rui Benedito, Beat Lutz, Tobias Bäuerle, Jens Hartwig, Jan Baumgart, Marcus Krüger, Konstantin Radyushkin, Lavinia Alberi, Benedikt Berninger, Mirko H H Schmidt
Adult neural stem cells reside in a specialized niche in the subventricular zone (SVZ). Throughout life they give rise to adult-born neurons in the olfactory bulb (OB), thus contributing to neural plasticity and pattern discrimination. Here, we show that the neurovascular protein EGFL7 is secreted by endothelial cells and neural stem cells (NSCs) of the SVZ to shape the vascular stem-cell niche. Loss of EGFL7 causes an accumulation of activated NSCs, which display enhanced activity and re-entry into the cell cycle...
June 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28648028/-expression-changes-of-notch-and-nuclear-factor-%C3%AE%C2%BAb-signaling-pathways-in-the-rat-heart-with-myocardial-infarction
#6
J L Jin, Z T Deng, R G Lyu, X H Liu, J R Wei
Objective: To observe the expression changes of Notch and nuclear factor-κB (NF-κB) signaling pathways in rat myocardium post myocardial infarction. Methods: Myocardial infarction was established by ligation of the left anterior descending coronary artery(MI group), sham rats (similar surgical procedure without coronary artery ligation) served as control, the rats were sacrificed at first week, 4th and 8th week after operation, the non-infarct myocardial tissue in both groups was obtained to detect the mRNA expression of Notch1, Dll4 and Hes1 by RT-PCR, the protein expression of NICD1 was detected by Western blot, the nuclear protein p65 content was detected to reflect the activation degree of NF-κB signaling in the cardiomyocytes...
June 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28623973/dynamic-maternal-and-fetal-notch-activity-and-expression-in-placentation
#7
Heather I Levin, Chantae S Sullivan-Pyke, Virginia E Papaioannou, Ronald J Wapner, Jan K Kitajewski, Carrie J Shawber, Nataki C Douglas
INTRODUCTION: Murine placentation requires trophoblast Notch2, while the Notch ligand, JAGGED1, is reduced in invasive trophoblasts from women with preeclampsia. However, the placental cells with active Notch signaling and expression of other Notch proteins and ligands in placentation have yet to be defined. We sought to identify endothelial cell and trophoblast subtypes with canonical Notch signaling in the decidua and placenta and correlate this to expression of Notch proteins and ligands...
July 2017: Placenta
https://www.readbyqxmd.com/read/28599454/differential-expression-of-the-notch1-receptor-and-its-ligands-dll1-dll3-and-dll4-in-distinct-human-pituitary-adenoma-subtypes
#8
Jianfu Zhang, Hua Gao, Yazhuo Zhang
Pituitary adenoma (PA) is a common type of benign tumor of the pituitary gland that is characterized by specific signs and symptoms, primarily associated with hypersecretion of pituitary glycoprotein hormones (thyroid-stimulating, growth and adrenocorticotrophic hormones, and prolactin). Surgery is the first-line treatment, although postoperative residual tissues/cells and subsequent recurrence remain notable complications. Gene therapy is an effective approach for treatment, as previous studies have demonstrated that the Notch signaling pathway participates in the pathogenesis of PA...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28567545/host-genetic-modifiers-of-nonproductive-angiogenesis-inhibit-breast-cancer
#9
Michael J Flister, Shirng-Wern Tsaih, Alexander Stoddard, Cody Plasterer, Jaidip Jagtap, Abdul K Parchur, Gayatri Sharma, Anthony R Prisco, Angela Lemke, Dana Murphy, Mona Al-Gizawiy, Michael Straza, Sophia Ran, Aron M Geurts, Melinda R Dwinell, Andrew S Greene, Carmen Bergom, Peter S LaViolette, Amit Joshi
PURPOSE: Multiple aspects of the tumor microenvironment (TME) impact breast cancer, yet the genetic modifiers of the TME are largely unknown, including those that modify tumor vascular formation and function. METHODS: To discover host TME modifiers, we developed a system called the Consomic/Congenic Xenograft Model (CXM). In CXM, human breast cancer cells are orthotopically implanted into genetically engineered consomic xenograft host strains that are derived from two parental strains with different susceptibilities to breast cancer...
May 31, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28542953/zebrafish-tmem230a-cooperates-with-the-delta-notch-signaling-pathway-to-modulate-endothelial-cell-number-in-angiogenic-vessels
#10
Silvia Carra, Lorenzo Sangiorgio, Paride Pelucchi, Solei Cermenati, Alessandra Mezzelani, Valentina Martino, Mira Palizban, Alberto Albertini, Martin Götte, James Kehler, Gianluca Deflorian, Monica Beltrame, Antonio Giordano, Rolland Reinbold, Franco Cotelli, Gianfranco Bellipanni, Ileana Zucchi
During embryonic development, new arteries, and veins form from preexisting vessels in response to specific angiogenic signals. Angiogenic signaling is complex since not all endothelial cells exposed to angiogenic signals respond equally. Some cells will be selected to become tip cells and acquire migration and proliferation capacity necessary for vessel growth while others, the stalk cells become trailer cells that stay connected with pre-existing vessels and act as a linkage to new forming vessels. Additionally, stalk and tip cells have the capacity to interchange their roles...
May 25, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28536097/dynamic-regulation-of-vegf-inducible-genes-by-an-erk-erg-p300-transcriptional-network
#11
Jason E Fish, Manuel Cantu Gutierrez, Lan T Dang, Nadiya Khyzha, Zhiqi Chen, Shawn Veitch, Henry S Cheng, Melvin Khor, Lina Antounians, Makon-Sébastien Njock, Emilie Boudreau, Alexander M Herman, Alexander M Rhyner, Oscar E Ruiz, George T Eisenhoffer, Alejandra Medina-Rivera, Michael D Wilson, Joshua D Wythe
The transcriptional pathways activated downstream of Vascular Endothelial Growth Factor (VEGF) signaling during angiogenesis remain incompletely characterized. By assessing the signals responsible for induction of the Notch ligand, Delta-Like 4 (DLL4) in endothelial cells we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. Furthermore, VEGF/ERK signaling induces phosphorylation and activation of the ETS transcription factor ERG, a prerequisite for DLL4 induction...
May 23, 2017: Development
https://www.readbyqxmd.com/read/28533486/galectin-3-acts-as-an-angiogenic-switch-to-induce-tumor-angiogenesis-via-jagged-1-notch-activation
#12
Sofia Nascimento Dos Santos, Helen Sheldon, Jonathas Xavier Pereira, Christopher Paluch, Esther M Bridges, Márcia Curry El-Cheikh, Adrian L Harris, Emerson Soares Bernardes
Angiogenesis is a coordinated process tightly regulated by the balance between Delta-like-4 (DLL4) and Jagged-1 (JAG1) in endothelial cells. Here we show that galectin-3 (gal-3), a glycan-binding protein secreted by cancer cells under hypoxic conditions, triggers sprouting angiogenesis, assisted by hypoxic changes in the glycosylation status of endothelial cells that enhance binding to gal-3. Galectin-3's proangiogenic functions were found to be predominantly dependent on the Notch ligand JAG1. Differential direct binding to JAG1 was shown by surface plasmon resonance assay...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533359/selective-regulation-of-notch-ligands-during-angiogenesis-is-mediated-by-vimentin
#13
Daniel Antfolk, Marika Sjöqvist, Fang Cheng, Kimmo Isoniemi, Camille L Duran, Adolfo Rivero-Muller, Christian Antila, Rasmus Niemi, Sebastian Landor, Carlijn V C Bouten, Kayla J Bayless, John E Eriksson, Cecilia M Sahlgren
Notch signaling is a key regulator of angiogenesis, in which sprouting is regulated by an equilibrium between inhibitory Dll4-Notch signaling and promoting Jagged-Notch signaling. Whereas Fringe proteins modify Notch receptors and strengthen their activation by Dll4 ligands, other mechanisms balancing Jagged and Dll4 signaling are yet to be described. The intermediate filament protein vimentin, which has been previously shown to affect vascular integrity and regenerative signaling, is here shown to regulate ligand-specific Notch signaling...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28520516/mesenchymal-stem-cell-migration-and-proliferation-are-mediated-by-hypoxia-inducible-factor-1%C3%AE-upstream-of-notch-and-sumo-pathways
#14
María Ciria, Nahuel A García, Imelda Ontoria-Oviedo, Hernán González-King, Rubén Carrero, José Luis De La Pompa, José Anastasio Montero, Pilar Sepúlveda
Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha (HIF-1α) stabilization improves several MSC functions, including cell adhesion, migration, and proliferation, thereby increasing their therapeutic potential. To further explore the mechanisms induced by HIF-1α in MSCs, we studied its relationship with Notch signaling and observed that overexpression of HIF-1α in MSCs increased protein levels of the Notch ligands Jagged 1-2 and Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this pathway was activated...
July 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28498863/notch-ligands-regulate-the-muscle-stem-like-state-ex-vivo-but-are-not-sufficient-for-retaining-regenerative-capacity
#15
Hiroshi Sakai, Sumiaki Fukuda, Miki Nakamura, Akiyoshi Uezumi, Yu-Taro Noguchi, Takahiko Sato, Mitsuhiro Morita, Harumoto Yamada, Kunihiro Tsuchida, Shahragim Tajbakhsh, So-Ichiro Fukada
Myogenic stem cells are a promising avenue for the treatment of muscular disorders. Freshly isolated muscle stem cells have a remarkable engraftment ability in vivo, but their cell number is limited. Current conventional culture conditions do not allow muscle stem cells to expand in vitro with their bona fide engraftment efficiency, requiring the improvement of culture procedures for achieving successful cell-therapy for muscle disorders. Here we expanded mouse muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to activate Notch signaling in vitro and to investigate whether these cells could retain their engraftment efficiency...
2017: PloS One
https://www.readbyqxmd.com/read/28482141/notch-pathway-is-active-during-osteogenic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-induced-by-pulsed-electromagnetic-fields
#16
Leila Bagheri, Agnese Pellati, Paola Rizzo, Giorgio Aquila, Leo Massari, Monica De Mattei, Alessia Ongaro
Pulsed electromagnetic fields (PEMFs) have been used to treat bone diseases, particularly non-union healing. Although it is known that PEMFs promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs), to date PEMF molecular mechanisms remain not clearly elucidated. The Notch signaling is a highly conserved pathway which regulates cell fate decisions and skeletal development. The aim of this study was to investigate if the known PEMF-induced osteogenic effects may involve the modulation of the Notch pathway...
May 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28472949/distinct-gene-expression-profiles-associated-with-notch-ligands-delta-like-4-and-jagged1-in-plaque-material-from-peripheral-artery-disease-patients-a-pilot-study
#17
Giorgio Aquila, Cinzia Fortini, Antonio Pannuti, Serena Delbue, Micaela Pannella, Marco Bruno Morelli, Cristiana Caliceti, Fausto Castriota, Monica de Mattei, Alessia Ongaro, Agnese Pellati, Pasquale Ferrante, Lucio Miele, Luigi Tavazzi, Roberto Ferrari, Paola Rizzo, Alberto Cremonesi
BACKGROUND: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients. METHODS: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy...
May 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28470301/notch-signaling-in-regulating-angiogenesis-in-a-3d-biomimetic-environment
#18
Yi Zheng, Shue Wang, Xufeng Xue, Alan Xu, Wei Liao, Alice Deng, Guohao Dai, Allen P Liu, Jianping Fu
Angiogenesis is a complex cellular process involving highly orchestrated invasion and organization of endothelial cells (ECs) in a three-dimensional (3D) environment. Recent evidence indicates that Notch signaling is critically involved in regulating specialized functions and distinct fates of ECs in newly formed vasculatures during angiogenesis. Here, we demonstrated, for the first time, the application of a microengineered biomimetic system to quantitatively investigate the role of Notch signaling in regulating early angiogenic sprouting and vasculature formation of ECs in a 3D extracellular matrix...
May 31, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28446798/novel-missense-mutation-in-dll4-in-a-japanese-sporadic-case-of-adams-oliver-syndrome
#19
Miwako Nagasaka, Mariko Taniguchi-Ikeda, Hidehito Inagaki, Yuya Ouchi, Daisuke Kurokawa, Keiji Yamana, Risa Harada, Kandai Nozu, Yoshitada Sakai, Sushil K Mishra, Yoshiki Yamaguchi, Ichiro Morikoka, Tatsushi Toda, Hiroki Kurahashi, Kazumoto Iijima
Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata with vascular anomalies such as congenital heart defects. The etiology of this syndrome has remained largely unknown but defective Notch signaling during vascular formation has been suggested. Here we describe a sporadic Japanese newborn case with clinically diagnosed AOS. Trio whole-exome sequencing identified a de novo, novel, heterozygous missense mutation in the Delta-like 4 ligand gene (DLL4 c...
April 27, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28445154/role-of-delta-like-4-in-jagged1-induced-tumour-angiogenesis-and-tumour-growth
#20
Chern Ein Oon, Esther Bridges, Helen Sheldon, Richard C A Sainson, Adrian Jubb, Helen Turley, Russell Leek, Francesca Buffa, Adrian L Harris, Ji-Liang Li
Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in tumour angiogenesis. They were shown to have opposite effects on mouse retinal and adult regenerative angiogenesis. In tumours, both ligands are upregulated but their relative effects and interactions in tumour biology, particularly in tumour response to therapeutic intervention are unclear. Here we demonstrate that DLL4 and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1 endothelial cells but had opposing effects on sprouting angiogenesis in vitro...
June 20, 2017: Oncotarget
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