scholarly journals Notch signalling in ischaemia-induced angiogenesis

2009 ◽  
Vol 37 (6) ◽  
pp. 1221-1227 ◽  
Author(s):  
Ayman Al Haj Zen ◽  
Paolo Madeddu
Keyword(s):  
Notch Pathway ◽  
Therapeutic Angiogenesis ◽  
Notch Signalling ◽  
Signalling Pathways ◽  
Sprouting Angiogenesis ◽  
Vessel Maturation ◽  
Reparative Process ◽  
Novel Targets

Notch signalling represents a key pathway essential for normal vascular development. Recently, great attention has been focused on the implication of Notch pathway components in postnatal angiogenesis and regenerative medicine. This paper critically reviews the most recent findings supporting the role of Notch in ischaemia-induced neovascularization. Notch signalling reportedly regulates several steps of the reparative process occurring in ischaemic tissues, including sprouting angiogenesis, vessel maturation, interaction of vascular cells with recruited leucocytes and skeletal myocyte regeneration. Further characterization of Notch interaction with other signalling pathways might help identify novel targets for therapeutic angiogenesis.

Interaction of the transforming growth factor-β and Notch signaling pathways in the regulation of granulosa cell proliferation

2016 ◽  
Vol 28 (12) ◽  
pp. 1873 ◽  
Author(s):  
Xiao-Feng Sun ◽  
Xing-Hong Sun ◽  
Shun-Feng Cheng ◽  
Jun-Jie Wang ◽  
Yan-Ni Feng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Growth Factor ◽  
Granulosa Cell ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Notch Pathway ◽  
Transforming Growth Factor Β ◽  
Notch Signalling ◽  
Signalling Pathways

The Notch and transforming growth factor (TGF)-β signalling pathways play an important role in granulosa cell proliferation. However, the mechanisms underlying the cross-talk between these two signalling pathways are unknown. Herein we demonstrated a functional synergism between Notch and TGF-β signalling in the regulation of preantral granulosa cell (PAGC) proliferation. Activation of TGF-β signalling increased hairy/enhancer-of-split related with YRPW motif 2 gene (Hey2) expression (one of the target genes of the Notch pathway) in PAGCs, and suppression of TGF-β signalling by Smad3 knockdown reduced Hey2 expression. Inhibition of the proliferation of PAGCs by N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT), an inhibitor of Notch signalling, was rescued by both the addition of ActA and overexpression of Smad3, indicating an interaction between the TGF-β and Notch signalling pathways. Co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assays were performed to identify the point of interaction between the two signalling pathways. CoIP showed direct protein–protein interaction between Smad3 and Notch2 intracellular domain (NICD2), whereas ChIP showed that Smad3 could be recruited to the promoter regions of Notch target genes as a transcription factor. Therefore, the findings of the present study support the idea that nuclear Smad3 protein can integrate with NICD2 to form a complex that acts as a transcription factor to bind specific DNA motifs in Notch target genes, such as Hey1 and Hey2, and thus participates in the transcriptional regulation of Notch target genes, as well as regulation of the proliferation of PAGCs.

Signalling pathways in schistosomes: novel targets for control interventions against schistosomiasis

2017 ◽  
Vol 1 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Pengfei Cai ◽  
Donald P. McManus ◽  
Hong You
Keyword(s):  
Functional Characterization ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Future Perspectives ◽  
Self Renewal ◽  
Physiological Processes ◽  
Growth Development ◽  
Novel Targets

Over the last decade, there has been accumulating evidence showing that signalling pathways are involved in extensive biological and physiological processes in the human blood fluke schistosomes, playing essential roles in environmental sensing, host penetration, growth, development, maturation, embryogenesis, tissue self-renewal and survival. Owing to the likelihood of resistance developing against praziquantel, the only drug currently available that is effective against all the human schistosome species, there is an urgent requirement for an alternative treatment, arguing for continuing research into novel or repurposed anti-schistosomal drugs. An increasing number of anticancer drugs are being developed which block abnormal signalling pathways, a feature that has stimulated interest in developing novel interventions against human schistosomiasis by targeting key cell signalling components. In this review, we discuss the functional characterization of signal transduction pathways in schistosomes and consider current challenges and future perspectives in this important area of research.

To sprout or to split? VEGF, Notch and vascular morphogenesis

2011 ◽  
Vol 39 (6) ◽  
pp. 1644-1648 ◽  
Author(s):  
Roberto Gianni-Barrera ◽  
Marianna Trani ◽  
Silvia Reginato ◽  
Andrea Banfi
Keyword(s):  
Therapeutic Angiogenesis ◽  
Notch Signalling ◽  
Molecular Regulation ◽  
Postnatal Life ◽  
Vascular Growth ◽  
Fundamental Factor ◽  
Sprouting Angiogenesis ◽  
Vascular Morphogenesis ◽  
Artery Disease ◽  
Endothelial Growth Factor

Therapeutic angiogenesis is an attractive strategy to treat patients suffering from peripheral or coronary artery disease. VEGF (vascular endothelial growth factor-A) is the fundamental factor controlling vascular growth in both development and postnatal life. The interplay between the VEGF and Notch signalling pathway has been recently found to regulate the morphogenic events leading to the growth of new vessels by sprouting. Angiogenesis can also take place by an alternative process, i.e. intussusception or vascular splitting. However, little is known about its role in therapeutic angiogenesis and its molecular regulation. In the present article, we briefly review how VEGF dose determines the induction of normal or aberrant angiogenesis and the molecular regulation of sprouting angiogenesis by Notch signalling, and compare this process with intussusception.

Two different activities of Suppressor of Hairless during wing development in Drosophila

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3553-3566 ◽  
Author(s):  
T. Klein ◽  
L. Seugnet ◽  
M. Haenlin ◽  
A. Martinez Arias
Keyword(s):  
Target Genes ◽  
Transmembrane Protein ◽  
Current Model ◽  
Notch Pathway ◽  
Notch Signalling ◽  
Wing Development ◽  
Transcription Activator ◽  
Cell Fates ◽  
H Protein

The Notch pathway plays a crucial and universal role in the assignation of cell fates during development. In Drosophila, Notch is a transmembrane protein that acts as a receptor of two ligands Serrate and delta. The current model of Notch signal transduction proposes that Notch is activated upon binding its ligands and that this leads to the cleavage and release of its intracellular domain (also called Nintra). Nintra translocates to the nucleus where it forms a dimeric transcription activator with the Su(H) protein. In contrast with this activation model, experiments with the vertebrate homologue of Su(H), CBF1, suggest that, in vertebrates, Nintra converts CBF1 from a repressor into an activator. Here we have assessed the role of Su(H) in Notch signalling during the development of the wing of Drosophila. Our results show that, during this process, Su(H) can activate the expression of some Notch target genes and that it can do so without the activation of the Notch pathway or the presence of Nintra. In contrast, the activation of other Notch target genes requires both Su(H) and Nintra, and, in the absence of Nintra, Su(H) acts as a repressor. We also find that the Hairless protein interacts with Notch signalling during wing development and inhibits the activity of Su(H). Our results suggest that, in Drosophila, the activation of Su(H) by Notch involve the release of Su(H) from an inhibitory complex, which contains the Hairless protein. After its release Su(H) can activate gene expression in absence of Nintra.

Notch signalling and the initiation of neural development in the Drosophila eye

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 3889-3898 ◽  
Author(s):  
Antonio Baonza ◽  
Matthew Freeman
Keyword(s):  
Neural Development ◽  
Notch Signalling ◽  
The Other ◽  
Signalling Pathways ◽  
Notch Signalling Pathway ◽  
Drosophila Eye ◽  
Dependent Signal ◽  
Notch Activation ◽  
Number Of Cells

Neural determination in the Drosophila eye occurs progressively. A diffusible signal, Dpp, causes undetermined cells first to adopt a ‘pre-proneural’ state in which they are primed to start differentiating. A second signal is required to trigger the activation of the transcription factor Atonal, which causes the cells to initiate overt photoreceptor neurone differentiation. Both Dpp and the second signal are dependent on Hedgehog (Hh) signalling. Previous work has shown that the Notch signalling pathway also has a proneural role in the eye (as well as a later, opposite function when it restricts the number of cells becoming photoreceptors – a process of lateral inhibition). It is not clear how the early proneural role of Notch integrates with the other signalling pathways involved. We provide evidence that Notch activation by its ligand Delta is the second Hh-dependent signal required for neural determination. Notch activity normally only triggers Atonal expression in cells that have adopted the pre-proneural state induced by Dpp. We also report that Notch drives the transition from pre-proneural to proneural by downregulating two repressors of Atonal: Hairy and Extramacrochaetae.

The role of presenilin 1 during somite segmentation

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1391-1402 ◽  
Author(s):  
K.i. Koizumi ◽  
M. Nakajima ◽  
S. Yuasa ◽  
Y. Saga ◽  
T. Sakai ◽  
...  
Keyword(s):  
Notch Pathway ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Paraxial Mesoderm ◽  
Presenilin 1 ◽  
Wild Type ◽  
Presomitic Mesoderm ◽  
Notch Signalling Pathway ◽  
Deficient Mice

The Notch signalling pathway plays essential roles during the specification of the rostral and caudal somite halves and subsequent segmentation of the paraxial mesoderm. We have re-investigated the role of presenilin 1 (Ps1; encoded by Psen1) during segmentation using newly generated alleles of the Psen1 mutation. In Psen1-deficient mice, proteolytic activation of Notch1 was significantly affected and the expression of several genes involved in the Notch signalling pathway was altered, including Δ-like3, Hes5, lunatic fringe (Lfng) and Mesp2. Thus, Ps1-dependent activation of the Notch pathway is essential for caudal half somite development. We observed defects in Notch signalling in both the caudal and rostral region of the presomitic mesoderm. In the caudal presomitic mesoderm, Ps1 was involved in maintaining the amplitude of cyclic activation of the Notch pathway, as represented by significant reduction of Lfng expression in Psen1-deficient mice. In the rostral presomitic mesoderm, rapid downregulation of the Mesp2 expression in the presumptive caudal half somite depends on Ps1 and is a prerequisite for caudal somite half specification. Chimaera analysis between Psen1-deficient and wild-type cells revealed that condensation of the wild-type cells in the caudal half somite was concordant with the formation of segment boundaries, while mutant and wild-type cells intermingled in the presomitic mesoderm. This implies that periodic activation of the Notch pathway in the presomitic mesoderm is still latent to segregate the presumptive rostral and caudal somite. A transient episode of Mesp2 expression might be needed for Notch activation by Ps1 to confer rostral or caudal properties. In summary, we propose that Ps1 is involved in the functional manifestation of the segmentation clock in the presomitic mesoderm.

scholarly journals Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis

2016 ◽  
Vol 75 (11) ◽  
pp. 2037-2044 ◽  
Author(s):  
Neng-Yu Lin ◽  
Alfiya Distler ◽  
Christian Beyer ◽  
Ariella Philipi-Schöbinger ◽  
Silvia Breda ◽  
...  
Keyword(s):  
Target Genes ◽  
Notch Pathway ◽  
Notch Signalling ◽  
Dependent Manner ◽  
Notch 1 ◽  
Chondrocyte Hypertrophy ◽  
Hedgehog Signalling ◽  
Osteophyte Formation

ObjectivesNotch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice.MethodsNotch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments.ResultsNotch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1.ConclusionsInhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA.

scholarly journals Endothelial-specific YY1 governs sprouting angiogenesis through directly interacting with RBPJ

2020 ◽  
Vol 117 (9) ◽  
pp. 4792-4801 ◽  
Author(s):  
Shuya Zhang ◽  
Ji Young Kim ◽  
Suowen Xu ◽  
Huan Liu ◽  
Meimei Yin ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cell Formation ◽  
Aortic Ring ◽  
Retinal Vessel ◽  
Sprouting Angiogenesis ◽  
Severe Impairment ◽  
Repression Complex ◽  
Vessel Maturation ◽  
And Migration

Angiogenesis, the formation of new blood vessels, is tightly regulated by gene transcriptional programs. Yin Ying 1 (YY1) is a ubiquitously distributed transcription factor with diverse and complex biological functions; however, little is known about the cell-type-specific role of YY1 in vascular development and angiogenesis. Here we report that endothelial cell (EC)-specificYY1deletion in mice led to embryonic lethality as a result of abnormal angiogenesis and vascular defects. Tamoxifen-inducible EC-specificYY1knockout (YY1iΔEC) mice exhibited a scarcity of retinal sprouting angiogenesis with fewer endothelial tip cells.YY1iΔECmice also displayed severe impairment of retinal vessel maturation. In an ex vivo mouse aortic ring assay and a human EC culture system, YY1 depletion impaired endothelial sprouting and migration. Mechanistically, YY1 functions as a repressor protein of Notch signaling that controls EC tip-stalk fate determination. YY1 deficiency enhanced Notch-dependent gene expression and reduced tip cell formation. Specifically, YY1 bound to the N-terminal domain of RBPJ (recombination signal binding protein for Ig Kappa J region) and competed with the Notch coactivator MAML1 (mastermind-like protein 1) for binding to RBPJ, thereby impairing the NICD (intracellular domain of the Notch protein)/MAML1/RBPJ complex formation. Our study reveals an essential role of endothelial YY1 in controlling sprouting angiogenesis through directly interacting with RBPJ and forming a YY1-RBPJ nuclear repression complex.

scholarly journals Histamine, Metabolic Remodelling and Angiogenesis: A Systems Level Approach

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 415
Author(s):  
Aurelio A. Moya-García ◽  
Almudena Pino-Ángeles ◽  
Francisca Sánchez-Jiménez ◽  
José Luis Urdiales ◽  
Miguel Ángel Medina
Keyword(s):  
Research Field ◽  
G Protein Coupled Receptors ◽  
Signalling Pathways ◽  
Histamine Metabolism ◽  
Current Information ◽  
Physiological Processes ◽  
Cell Growth And Differentiation ◽  
G Protein Coupled

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. Histamine metabolism conforms a very complex network that connect many metabolic processes important for homeostasis, including nitrogen and energy metabolism. This review brings together and analyses the current information on the relationships of the “histamine system” with other important metabolic modules in human physiology, aiming to bridge current information gaps. In this regard, the molecular characterization of the role of histamine in the modulation of angiogenesis-mediated processes, such as cancer, makes a promising research field for future biomedical advances.

Digital x-ray mapping of nanometer-size supported bimetallic catalysts

1988 ◽  
Vol 46 ◽  
pp. 530-531
Author(s):  
L. T. Germinario
Keyword(s):  
Background Radiation ◽  
Metal Cluster ◽  
Single Element ◽  
Beam Diameter ◽  
X Rays ◽  
X Ray ◽  
Major Interest ◽  
Induced Changes

Understanding the role of metal cluster composition in determining catalytic selectivity and activity is of major interest in heterogeneous catalysis. The electron microscope is well established as a powerful tool for ultrastructural and compositional characterization of support and catalyst. Because the spatial resolution of x-ray microanalysis is defined by the smallest beam diameter into which the required number of electrons can be focused, the dedicated STEM with FEG is the instrument of choice. The main sources of errors in energy dispersive x-ray analysis (EDS) are: (1) beam-induced changes in specimen composition, (2) specimen drift, (3) instrumental factors which produce background radiation, and (4) basic statistical limitations which result in the detection of a finite number of x-ray photons. Digital beam techniques have been described for supported single-element metal clusters with spatial resolutions of about 10 nm. However, the detection of spurious characteristic x-rays away from catalyst particles produced images requiring several image processing steps.

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