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https://www.readbyqxmd.com/read/28087639/vegfd-modulates-both-angiogenesis-and-lymphangiogenesis-during-zebrafish-embryonic-development
#1
Neil I Bower, Adam J Vogrin, Ludovic Le Guen, Huijun Chen, Steven A Stacker, Marc G Achen, Benjamin M Hogan
Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, the formation of veins and lymphatics. VEGFD has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#2
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28077598/notch-ligand-delta-like-4-promotes-regulatory-t-cell-identity-in-pulmonary-viral-infection
#3
Hung-An Ting, Matthew A Schaller, Denise E de Almeida Nagata, Andrew J Rasky, Ivan P Maillard, Nicholas W Lukacs
Regulatory T (Treg) cells establish tolerance, prevent inflammation at mucosal surfaces, and regulate immunopathology during infectious responses. Recent studies have shown that Delta-like ligand 4 (Dll4) was upregulated on APC after respiratory syncytial virus (RSV) infection, and its inhibition leads to exaggerated immunopathology. In the present study, we outline the role of Dll4 in Treg cell differentiation, stability, and function in RSV infection. We found that Dll4 was expressed on CD11b(+) pulmonary dendritic cells in the lung and draining lymph nodes in wild-type BALB/c mice after RSV infection...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28058628/a-pilot-study-on-plasma-levels-of-micro-rnas-involved-in-angiogenesis-and-vascular-maturation-in-patients-with-breast-cancer
#4
Emmanuel Kontomanolis, Achilleas Mitrakas, Alexandra Giatromanolaki, Dimitra Kareli, Marianthi Panteliadou, Stamatia Pouliliou, Michael I Koukourakis
Micro-RNAs (miRNAs) have a complex role in carcinogenesis and tumour progression. Several miRNAs, such as miR-221, miR-27b and miR-132, have been implicated in the regulation of VEGF tumour angiogenic activity. In this pilot study, we assessed angiogenesis and DLL4+ vascular maturation index (VMI) in breast cancer tissues, in parallel with the plasma levels of the above-mentioned miRNAs. Significantly higher than control samples pre-operative levels were recorded in 10/11, 7/11 and 9/11 cases for the miR-221, miR-27b and miR-132, respectively...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/27999190/leptin-notch-signaling-axis-is-involved-in-pancreatic-cancer-progression
#5
Adriana Harbuzariu, Antonio Rampoldi, Danielle S Daley-Brown, Pierre Candelaria, Tia L Harmon, Crystal C Lipsey, Derrick J Beech, Alexander Quarshie, Gabriela Oprea Ilies, Ruben R Gonzalez-Perez
Pancreatic cancer (PC) shows a high death rate. PC incidence and prognosis are affected by obesity, a pandemic characterized by high levels of leptin. Notch is upregulated by leptin in breast cancer. Thus, leptin and Notch crosstalk could influence PC progression. Here we investigated in PC cell lines (BxPC-3, MiaPaCa-2, Panc-1, AsPC-1), derived tumorspheres and xenografts whether a functional leptin-Notch axis affects PC progression and expansion of pancreatic cancer stem cells (PCSC). PC cells and tumorspheres were treated with leptin and inhibitors of Notch (gamma-secretase inhibitor, DAPT) and leptin (iron oxide nanoparticle-leptin peptide receptor antagonist 2, IONP-LPrA2)...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27982686/the-expression-levels-of-notch-related-signaling-molecules-in-pulmonary-microvascular-endothelial-cells-in-bleomycin-induced-rat-pulmonary-fibrosis
#6
Qian Yin, Weihua Wang, Guangbin Cui, Haiyan Nan, Linfeng Yan, Wenhu Zhang, Song Zhang, Jingguo Wei
Previous studies have suggested that the Notch signaling pathway plays a very important role in the proliferation and differentiation of pulmonary microvascular endothelial cells (PMVECs). Therefore, we aimed to investigate the expression level of Notch-related signaling molecules in PMVECs in bleomycin (BLM)-induced rat pulmonary fibrosis. Immunohistochemistry, immunofluorescence, western blotting, and real-time PCR were used to analyze the differences in protein and mRNA expression levels of Notch-related signaling molecules, i...
December 16, 2016: Physiological Research
https://www.readbyqxmd.com/read/27939883/indispensable-role-of-notch-ligand-dependent-signaling-in-the-proliferation-and-stem-cell-niche-maintenance-of-apc-deficient-intestinal-tumors
#7
Toru Nakata, Hiromichi Shimizu, Sayaka Nagata, Go Ito, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Fumiaki Ishibashi, Reiko Kuno, Sho Anzai, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Katsuto Hozumi, Mamoru Watanabe, Ryuichi Okamoto
Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5(+ve) cells of APC-deficient mice intestinal tumors. Accordingly, Notch ligands, including Jag1, Dll1, and Dll4, were expressed in these tumors...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27939630/endosulfan-inhibits-proliferation-through-the-notch-signaling-pathway-in-human-umbilical-vein-endothelial-cells
#8
Jialiu Wei, Lianshuang Zhang, Lihua Ren, Jin Zhang, Yang Yu, Ji Wang, Junchao Duan, Cheng Peng, Zhiwei Sun, Xianqing Zhou
Our previous research showed that endosulfan triggers the extrinsic coagulation pathway by damaging endothelial cells and causes hypercoagulation of blood. To identify the mechanism of endosulfan-impaired endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) with different concentrations of endosulfan, with and without an inhibitor for Notch, N-[N-(3, 5-difluorophenacetyl)-1-alanyl]S-Phenylglycinet-butylester (DAPT, 20 μM), or a reactive oxygen species (ROS) scavenger, N-Acetyl-l-cysteine (NAC, 3 mM), for 24 h...
February 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27933064/systemic-expression-of-notch-ligand-delta-like-4-during-mycobacterial-infection-alters-the-t-cell-immune-response
#9
Matthew A Schaller, Ronald M Allen, Soichiro Kimura, Cheryl L Day, Steven L Kunkel
The Notch ligand delta-like 4 (DLL4) is known to fine-tune the CD4(+) T cell cytokine response. DLL4 is expressed on the surface of antigen-presenting cells (APCs) in a MyD88-dependent manner. We found that DLL4 expression was upregulated on bone marrow progenitor cells and APCs in mice infected with BCG Mycobacterium. Transfer of DLL4(+) progenitor cells from infected hosts resulted in an increase DLL4(+) myeloid cells in the spleen, indicating that expression of the dll4 gene is propagated throughout hematopoiesis...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27929540/inflammation-and-notch-signaling-a-crosstalk-with-opposite-effects-on-tumorigenesis
#10
REVIEW
Chiara Fazio, Luigi Ricciardiello
The Notch cascade is a fundamental and highly conserved pathway able to control cell-fate. The Notch pathway arises from the interaction of one of the Notch receptors (Notch1-4) with different types of ligands; in particular, the Notch pathway can be activated canonically (through the ligands Jagged1, Jagged2, DLL1, DLL3 or DLL4) or non-canonically (through various molecules shared by other pathways). In the context of tumor biology, the deregulation of Notch signaling is found to be crucial, but it is still not clear if the activation of this pathway exerts a tumor-promoting or a tumor suppressing function in different cancer settings...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#11
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27919854/jagged1-and-dll4-expressions-in-benign-and-malignant-pancreatic-lesions-and-their-clinicopathological-significance
#12
Sheng-Fu Huang, Zhu-Lin Yang, Dai-Qiang Li, Zhi-Yu Liu, Chun-Wei Wang, Xiong-Ying Miao, Qiong Zou, Yuan Yuan
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC. METHODS: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals...
December 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/27898698/myeloid-dll4-does-not-contribute-to-the-pathogenesis-of-non-alcoholic-steatohepatitis-in-ldlr-mice
#13
Mike L J Jeurissen, Sofie M A Walenbergh, Tom Houben, Tim Hendrikx, Jieyi Li, Yvonne Oligschlaeger, Patrick J van Gorp, Marion J J Gijbels, Albert Bitorina, Isabell Nessel, Freddy Radtke, Marc Vooijs, Jan Theys, Ronit Shiri-Sverdlov
Non-alcoholic steatohepatitis (NASH) is characterized by liver steatosis and inflammation. Currently, the underlying mechanisms leading to hepatic inflammation are not fully understood and consequently, therapeutic options are poor. Non-alcoholic steatohepatitis (NASH) and atherosclerosis share the same etiology whereby macrophages play a key role in disease progression. Macrophage function can be modulated via activation of receptor-ligand binding of Notch signaling. Relevantly, global inhibition of Notch ligand Delta-Like Ligand-4 (DLL4) attenuates atherosclerosis by altering the macrophage-mediated inflammatory response...
2016: PloS One
https://www.readbyqxmd.com/read/27898394/mef2-transcription-factors-are-key-regulators-of-sprouting-angiogenesis
#14
Natalia Sacilotto, Kira M Chouliaras, Leonid L Nikitenko, Yao Wei Lu, Martin Fritzsche, Marsha D Wallace, Svanhild Nornes, Fernando García-Moreno, Sophie Payne, Esther Bridges, Ke Liu, Daniel Biggs, Indrika Ratnayaka, Shane P Herbert, Zoltán Molnár, Adrian L Harris, Benjamin Davies, Gareth L Bond, George Bou-Gharios, John J Schwarz, Sarah De Val
Angiogenesis, the fundamental process by which new blood vessels form from existing ones, depends on precise spatial and temporal gene expression within specific compartments of the endothelium. However, the molecular links between proangiogenic signals and downstream gene expression remain unclear. During sprouting angiogenesis, the specification of endothelial cells into the tip cells that lead new blood vessel sprouts is coordinated by vascular endothelial growth factor A (VEGFA) and Delta-like ligand 4 (Dll4)/Notch signaling and requires high levels of Notch ligand DLL4...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27891816/dll4-overexpression-increases-gastric-cancer-stem-progenitor-cell-self-renewal-ability-and-correlates-with-poor-clinical-outcome-via-notch-1-signaling-pathway-activation
#15
Zhi-Feng Miao, Hao Xu, Hui-Mian Xu, Zhen-Ning Wang, Ting-Ting Zhao, Yong-Xi Song, Ying-Ying Xu
Gastric cancer is one of the most common malignant diseases, and poses a serious threat to the quality of human life. Gastric cancer stem/progenitor cells (GCSPCs) have critical effects on tumor formation, affecting specific features of self-renewal and differentiation and playing a critical role in metastasis. The Notch-1 pathway is crucially important to GCSPCs and is regulated by DLL4. In this study, DLL4 and Nestin levels were measured in 383 gastric cancer tissue samples by immunohistochemistry, and the clinico-pathological features of patients assessed...
November 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27880939/inhibition-of-the-transcriptional-repressor-complex-bcl-6-bcor-induces-endothelial-sprouting-but-does-not-promote-tumor-growth
#16
Elisabeth Buchberger, Dietmar Payrhuber, Miriam El Harchi, Branislav Zagrapan, Katharina Scheuba, Anna Zommer, Edina Bugyik, Balazs Dome, Julia Barbara Kral, Waltraud Cornelia Schrottmaier, Gernot Schabbauer, Peter Petzelbauer, Marion Gröger, Martin Bilban, Christine Brostjan
The oncogenic potential of the transcriptional repressor Bcl-6 (B-cell lymphoma 6) was originally discovered in non-Hodgkin patients and the soluble Bcl-6 inhibitor 79-6 was developed to treat diffuse large B-cell lymphomas with aberrant Bcl-6 expression. Since we found Bcl-6 and its co-repressor BCoR (Bcl-6 interacting co-repressor) to be regulated in human microvascular endothelium by colorectal cancer cells, we investigated their function in sprouting angiogenesis which is central to tumor growth. Based on Bcl-6/BCoR gene silencing we found that the transcriptional repressor complex in fact constitutes an endogenous inhibitor of vascular sprouting by supporting the stalk cell phenotype: control of Notch target genes (HES1, HEY1, DLL4) and cell cycle regulators (cyclin A and B1)...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27870831/asymmetric-division-coordinates-collective-cell-migration-in-angiogenesis
#17
Guilherme Costa, Kyle I Harrington, Holly E Lovegrove, Donna J Page, Shilpa Chakravartula, Katie Bentley, Shane P Herbert
The asymmetric division of stem or progenitor cells generates daughters with distinct fates and regulates cell diversity during tissue morphogenesis. However, roles for asymmetric division in other more dynamic morphogenetic processes, such as cell migration, have not previously been described. Here we combine zebrafish in vivo experimental and computational approaches to reveal that heterogeneity introduced by asymmetric division generates multicellular polarity that drives coordinated collective cell migration in angiogenesis...
November 21, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27846305/time-to-decide-dynamical-analysis-predicts-partial-tip-stalk-patterning-states-arise-during-angiogenesis
#18
Lakshmi Venkatraman, Erzsébet Ravasz Regan, Katie Bentley
Angiogenesis is a highly dynamic morphogenesis process; however, surprisingly little is known about the timing of the different molecular processes involved. Although the role of the VEGF-notch-DLL4 signaling pathway has been established as essential for tip/stalk cell competition during sprouting, the speed and dynamic properties of the underlying process at the individual cell level has not been fully elucidated. In this study, using mathematical modeling we investigate how specific, biologically meaningful, local conditions around and within an individual cell can influence their unique tip/stalk phenotype switching kinetics...
2016: PloS One
https://www.readbyqxmd.com/read/27780917/the-somite-secreted-factor-maeg-promotes-zebrafish-embryonic-angiogenesis
#19
Xin Wang, Wei Yuan, Xueqian Wang, Jialing Qi, Yinyin Qin, Yunwei Shi, Jie Zhang, Jie Gong, Zhangji Dong, Xiaoyu Liu, Chen Sun, Renjie Chai, Ferdinand Le Noble, Dong Liu
MAM and EGF containing gene (MAEG), also called Epidermal Growth Factor-like domain multiple 6 (EGFL6), belongs to the epidermal growth factor repeat superfamily. The role of Maeg in zebrafish angiogenesis remains unclear. It was demonstrated that maeg was dynamically expressed in zebrafish developing somite during a time window encompassing many key steps in embryonic angiogenesis. Maeg loss-of-function embryos showed reduced endothelial cell number and filopodia extensions of intersegmental vessels (ISVs)...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27758766/fzd7-frizzled-7-expressed-by-endothelial-cells-controls-blood-vessel-formation-through-wnt-%C3%AE-catenin-canonical-signaling
#20
Claire Peghaire, Marie Lise Bats, Raj Sewduth, Sylvie Jeanningros, Beatrice Jaspard, Thierry Couffinhal, Cécile Duplàa, Pascale Dufourcq
OBJECTIVE: Vessel formation requires precise orchestration of a series of morphometric and molecular events controlled by a multitude of angiogenic factors and morphogens. Wnt/frizzled signaling is required for proper vascular formation. In this study, we investigated the role of the Fzd7 (frizzled-7) receptor in retinal vascular development and its relationship with the Wnt/β-catenin canonical pathway and Notch signaling. APPROACH AND RESULTS: Using transgenic mice, we demonstrated that Fzd7 is required for postnatal vascular formation...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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