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https://www.readbyqxmd.com/read/29160307/a-non-canonical-notch-complex-regulates-adherens-junctions-and-vascular-barrier-function
#1
William J Polacheck, Matthew L Kutys, Jinling Yang, Jeroen Eyckmans, Yinyu Wu, Hema Vasavada, Karen K Hirschi, Christopher S Chen
The vascular barrier that separates blood from tissues is actively regulated by the endothelium and is essential for transport, inflammation, and haemostasis1. Haemodynamic shear stress plays a critical role in maintaining endothelial barrier function2, but how this occurs remains unknown. Here, using an engineered organotypic model of perfused microvessels and confirming in mouse models, we identify that activation of the Notch1 transmembrane receptor directly regulates vascular barrier function through a non-canonical, transcription independent signalling mechanism that drives adherens junction assembly...
November 13, 2017: Nature
https://www.readbyqxmd.com/read/29139170/single-cell-resolution-of-human-hemato-endothelial-cells-defines-transcriptional-signatures-of-hemogenic-endothelium
#2
Mathew G Angelos, Juan E Abrahante, Robert H Blum, Dan S Kaufman
Endothelial-to-hematopoietic transition (EHT) is an important stage in definitive hematopoietic development. However, the genetic mechanisms underlying human EHT remains poorly characterized. We performed single cell RNA-seq using 55 hemogenic endothelial cells (HE: CD31(+) CD144(+) CD41(-) CD43(-) CD45(-) CD73(-) RUNX1c(+) ), 47 vascular endothelial cells without hematopoietic potential (non-HE: CD31(+) CD144(+) CD41(-) CD43(-) CD45(-) CD73(-) RUNX1c(-) ), and 35 hematopoietic progenitor cells (HP: CD34(+) CD43(+) RUNX1c(+) ) derived from human embryonic stem cells (hESCs)...
November 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/29103459/protective-effect-of-shouwu-yizhi-decoction-against-vascular-dementia-by-promoting-angiogenesis
#3
Xiao-Ni Yang, Chang-Sheng Li, Chao Chen, Xiao-Yong Tang, Guang-Qing Cheng, Xia Li
Shouwu is a traditional Chinese medicine (TCM) with neuroprotective effect. Shouwu Yizhi decoction (SYD) was designed based on TCM theory. However, little is known about the roles of SYD in Vascular dementia (VaD). The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion (I/R) rat model to induce VaD. SYD administration (54 mg·kg(-1)) for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion (MCAO) rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test...
October 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29096712/crosstalk-between-h9n2-avian-influenza-virus-and-crypt-derived-intestinal-organoids
#4
Lulu Huang, Qihang Hou, Lulu Ye, Qian Yang, Qinghua Yu
The spread of Avian influenza virus via animal feces makes the virus difficult to prevent, which causes great threat to human health. Therefore, it is imperative to understand the survival and invasion mechanism of H9N2 virus in the intestinal mucosa. In this study, we used mouse threedimensional intestinal organoids that contained intestinal crypts and villi differentiated from intestinal stem cells to explore interactions between H9N2 avian influenza virus and the intestinal mucosa. The HA, NA, NP and PB1 genes of H9N2 viruses could be detected in intestinal organoids at 1 h, and reached peak levels at 48 h post-infection...
November 2, 2017: Veterinary Research
https://www.readbyqxmd.com/read/29068587/the-notch-signaling-pathway-in-head-and-neck-squamous-cell-carcinoma-a-meta-analysis
#5
REVIEW
Yu-Yue Zhao, Guang-Tao Yu, Ting Xiao, Jian Hu
BACKGROUND: The Notch signaling pathway has been associated with the regulation of self-renewal capacity, cell cycle exit, and survival. However, the relationship between the Notch signaling pathway and HNSCC remains controversial. OBJECTIVES: A meta-analysis was conducted to evaluate the role of Notch signaling pathway in HNSCC. MATERIAL AND METHODS: Relevant studies published until March 31, 2015 were identified by searching the PubMed, EMBASE and Ovid database...
August 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29054964/gene-expression-profiling-of-the-notch-ahr-il22-axis-at-homeostasis-and-in-response-to-tissue-injury
#6
Marc Weidenbusch, Severin Rodler, Shangqing Song, Simone Romoli, Julian A Marschner, Franziska Kraft, Alexander Holderied, Santosh Kumar, Shrikant R Mulay, Mohsen Honarpisheh, Satish Kumar Devarapu, Maciej Lech, Hans-Joachim Anders
Notch and Interleukin-22 signaling are known to regulate tissue homeostasis and response to injury in humans and mice, and the induction of endogenous arylhydrocarbon receptor ligands through Notch links the two pathways in a hierarchical fashion. However, in adults the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TACE, PSEN1, BSG/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in 10 mature murine and human organs...
October 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#7
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29042972/expression-and-association-of-vegf-notch-pathways-in-infantile-hemangiomas
#8
Shangbin Li, Guangqi Xu, Feng Gao, Jianhai Bi, Ran Huo
The vascular endothelial growth factor (VEGF) and Notch signaling pathways have been identified to be involved in the neovascularization, and angiogenesis of various tumor types. However, there is little data regarding their roles and association in infantile hemangiomas (IHs). In the present study, the significance and association of the VEGF-VEGF receptor (R)2, and δ like canonical Notch ligand 4 (Dll4)-Notch1 pathways in different clinical phases of IHs were investigated. Specimens in the proliferating phase (n=15) and involuting phase (n=12) were collected...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042443/mammalian-numb-protein-antagonizes-notch-by-controlling-postendocytic-trafficking-of-the-notch-ligand-delta-like-4
#9
Ximing Shao, Zhihao Ding, Ming Zhao, Ke Liu, Haiyan Sun, Juntao Chen, Xianming Liu, Yuzhen Zhang, Yang Hong, Huashun Li, Hongchang Li
The biological antagonism between the signaling proteins Numb and Notch has been implicated in the regulation of many developmental processes, especially in asymmetric cell division. Mechanistic studies show that Numb inactivates Notch via endocytosis and proteasomal degradation that directly reduce Notch protein levels at the cell surface. However, some aspects of how Numb antagonizes Notch remain unclear. Here, we report a novel mechanism in which Numb acts as a Notch antagonist by controlling the intracellular destination and stability of the Notch ligand Delta-like 4 (Dll4) through a postendocytic-sorting process...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29037123/ultrafine-particle-exposure-reveals-the-importance-of-foxo1-notch-activation-complex-for-vascular-regeneration
#10
Kyung In Baek, René R Sevag Packard, Jeffrey J Hsu, Arian Saffari, Zhao Ma, Anh Phuong Luu, Andrew Pietersen, Hilary Yen, Bin Ren, Yichen Ding, Constantinos Sioutas, Rongsong Li, Tzung K Hsiai
AIMS: Redox active ultrafine particles (UFP, d < 0.2 μm) promote vascular oxidative stress and atherosclerosis. Notch signaling is intimately involved in vascular homeostasis, in which forkhead box O1 (FOXO1) acts as a co-activator of the Notch activation complex. We elucidated the importance of FOXO1/Notch transcriptional activation complex to restore vascular regeneration after UFP exposure. RESULTS: In a zebrafish model of tail injury and repair, transgenic Tg(fli1:GFP) embryos developed vascular regeneration at 3 days post amputation (dpa), whereas UFP exposure impaired regeneration (p < 0...
November 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29036275/porcupine-dependent-wnt-activity-within-the-uterine-epithelium-is-essential-for-fertility
#11
Omar Farah, Steffen Biechele, Janet Rossant, Daniel Dufort
The secretion of mammalian Wnt ligands within the cell is dependent on the activity of Porcupine, a gene located on the X-chromosome that encodes for a membrane bound o-acyl transferase. Here, we report that post-natal ablation of Porcupine in the uterine luminal epithelium alone results in the decrease in endometrial gland number. Despite having uterine glands, mutant females are completely infertile. Epithelial ablation of Porcupine causes defects in timely apposition of the lumen, along with failure to respond to artificial decidual induction...
October 4, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29032399/evidence-of-extracellular-vesicles-biogenesis-and-release-in-mouse-embryonic-stem-cells
#12
Lilian Cruz, Jenny Andrea Arevalo Romero, Mariana Brandão Prado, Tiago G Santos, Marilene Hohmuth Lopes
Extracellular vesicles (EVs) released by mouse embryonic stem cells (mESCs) are considered a source of bioactive molecules that modulate their microenvironment by acting on intercellular communication. Either intracellular endosomal machinery or their derived EVs have been considered a relevant system of signal circuits processing. Herein, we show that these features are found in mESCs. Ultrastructural analysis revealed structures and organelles of the endosomal system such as coated pits and endocytosis-related vesicles, prominent rough endoplasmic reticulum and Golgi apparatus, and multivesicular bodies (MVBs) containing either few or many intraluminal vesicles (ILVs) that could be released as exosomes to extracellular milieu...
October 14, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28981750/prospect-of-divergent-roles-for-the-cul3-system-in-vascular-endothelial-cell-function-and-angiogenesis
#13
REVIEW
Tomohisa Sakaue, Masashi Maekawa, Hironao Nakayama, Shigeki Higashiyama
Tissue remodelling and regeneration in various pathophysiological conditions (e.g. the processes of development, pregnancy, inflammation, wound healing, tissue regeneration, tumor growth, etc.) require angiogenesis, a dynamically coordinated response to stimuli from the extracellular microenvironment. During angiogenic and angiostatic responses, endothelial cells play a central role in the blood vessel formation and regression. Angiostatic responses, which are evoked by crucial factors such as VEGF and DLL4, have been elucidated...
October 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28973643/tacrolimus-rescues-the-signaling-and-gene-expression-signature-of-endothelial-alk1-loss-of-function-and-improves-hht-vascular-pathology
#14
Santiago Ruiz, Pallavi Chandakkar, Haitian Zhao, Julien Papoin, Prodyot K Chatterjee, Erica Christen, Christine N Metz, Lionel Blanc, Fabien Campagne, Philippe Marambaud
Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genetic vascular disorder arising from endothelial cell (EC) proliferation and hypervascularization, for which no cure exists. Because HHT is caused by loss-of-function mutations in BMP9-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. We interrogated the whole-transcriptome in human umbilical vein ECs (HUVECs) and found that ALK1 signaling inhibition was associated with a specific pro-angiogenic gene expression signature, which included a significant elevation of DLL4 expression...
September 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28946938/ldb2-regulates-the-expression-of-dll4-through-the-formation-of-oligomeric-complexes-in-endothelial-cells
#15
Hyun-Jung Choi, Seung-Sik Rho, Dong-Hoon Choi, Young-Guen Kwon
Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish...
September 26, 2017: BMB Reports
https://www.readbyqxmd.com/read/28925392/atypical-e2fs-inhibit-tumor-angiogenesis
#16
B G M W Weijts, B Westendorp, B T Hien, L M Martínez-López, M Zijp, I Thurlings, R E Thomas, S Schulte-Merker, W J Bakker, A de Bruin
Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28924218/uncontrolled-angiogenic-precursor-expansion-causes-coronary-artery-anomalies-in-mice-lacking-pofut1
#17
Yidong Wang, Bingruo Wu, Pengfei Lu, Donghong Zhang, Brian Wu, Shweta Varshney, Gonzalo Del Monte-Nieto, Zhenwu Zhuang, Rabab Charafeddine, Adam H Kramer, Nicolas E Sibinga, Nikolaos G Frangogiannis, Richard N Kitsis, Ralf H Adams, Kari Alitalo, David J Sharp, Richard P Harvey, Pamela Stanley, Bin Zhou
Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923397/the-two-novel-dll4-targeting-antibody-drug-conjugates-mvm03-and-mgd03-show-potent-anti-tumour-activity-in-breast-cancer-xenograft-models
#18
Shijing Wang, Rihong Zhou, Fumou Sun, Renjie Li, Min Wang, Min Wu
The anti-human Delta-like 4 (DLL4) monoclonal antibody MMGZ01 has a high affinity to hrDLL4 and arrests the DLL4-mediated human umbilical vein endothelial cell (HUVEC) phenotype, promotes immature vessels, and effectively reduces breast cancer cell growth in vivo. To develop a much more effective therapy, we conjugated MMGZ01 with two small-molecule cytotoxic agents, i.e., monomethyl auristatin E (MMAE) and doxorubicin (DOX), with different linkers to generate antibody-drug conjugates (ADCs), i.e., MMGZ01-vc-MMAE (named MvM03) and MMGZ01-GMBS-DOX (named MGD03), that are more potent therapeutic agents than naked antibody therapeutic agents...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28846711/identification-of-novel-biomarkers-to-monitor-%C3%AE-cell-function-and-enable-early-detection-of-type-2-diabetes-risk
#19
Kirstine J Belongie, Ele Ferrannini, Kjell Johnson, Patricia Andrade-Gordon, Michael K Hansen, John R Petrie
A decline in β-cell function is a prerequisite for the development of type 2 diabetes, yet the level of β-cell function in individuals at risk of the condition is rarely measured. This is due, in part, to the fact that current methods for assessing β-cell function are inaccurate, prone to error, labor-intensive, or affected by glucose-lowering therapy. The aim of the current study was to identify novel circulating biomarkers to monitor β-cell function and to identify individuals at high risk of developing β-cell dysfunction...
2017: PloS One
https://www.readbyqxmd.com/read/28839276/corrigendum-novel-missense-mutation-in-dll4-in-a-japanese-sporadic-case-of-adams-oliver-syndrome
#20
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 Morioka, Tatsushi Toda, Hiroki Kurahashi, Kazumoto Iijima
This corrects the article DOI: 10.1038/jhg.2017.48.
September 2017: Journal of Human Genetics
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