| Glycogen synthase kinase 3 beta positively regulates Notch signaling in vascular smooth muscle cells: role in cell proliferation and survival. | |
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MedLine Citation:
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PMID: 21557011 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of glycogen synthase kinase 3 beta (GSK-3β) in modulating Notch control of vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) was examined in vitro under varying conditions of cyclic strain and validated in vivo following changes in medial tension and stress. Modulation of GSK-3β in vSMC following ectopic expression of constitutively active GSK-3β, siRNA knockdown and pharmacological inhibition with SB-216763 demonstrated that GSK-3β positively regulates Notch intracellular domain expression, CBF-1/RBP-Jκ transactivation and downstream target gene mRNA levels, while concomitantly promoting vSMC proliferation and inhibiting apoptosis. In contrast, inhibition of GSK-3β attenuated Notch signaling and decreased vSMC proliferation and survival. Exposure of vSMC to cyclic strain environments in vitro using both a Flexercell™ Tension system and a novel Sylgard™ phantom vessel following bare metal stent implantation revealed that cyclic strain inhibits GSK-3β activity independent of p42/p44 MAPK and p38 activation concomitant with reduced Notch signaling and decreased vSMC proliferation and survival. Exposure of vSMC to changes in medial strain microenvironments in vivo following carotid artery ligation revealed that enhanced GSK-3β activity was predominantly localized to medial and neointimal vSMC concomitant with increased Notch signaling, proliferating nuclear antigen and decreased Bax expression, respectively, as vascular remodeling progressed. GSK-3β is an important modulator of Notch signaling leading to altered vSMC cell growth where low strain/tension microenvironments prevail. |
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Authors:
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Shaunta Guha; John P Cullen; David Morrow; Alberto Colombo; Caitríona Lally; Dermot Walls; Eileen M Redmond; Paul A Cahill |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-05-10 |
Journal Detail:
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Title: Basic research in cardiology Volume: 106 ISSN: 1435-1803 ISO Abbreviation: Basic Res. Cardiol. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-04 Completed Date: 2012-01-18 Revised Date: 2013-02-28 |
Medline Journal Info:
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Nlm Unique ID: 0360342 Medline TA: Basic Res Cardiol Country: Germany |
Other Details:
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Languages: eng Pagination: 773-85 Citation Subset: IM |
Affiliation:
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Vascular Health Research Centre, Faculty of Science and Health, Dublin City University, Dublin 9, Ireland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology* Biomechanics Cell Proliferation* Cell Survival / physiology Cells, Cultured Glycogen Synthase Kinase 3 / physiology* Mice Models, Animal Muscle, Smooth, Vascular / cytology, physiology* Neointima / physiopathology Rats Receptors, Notch / physiology* Signal Transduction / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AA-12610/AA/NIAAA NIH HHS; K99 HL095650/HL/NHLBI NIH HHS; K99HL095650/HL/NHLBI NIH HHS; R01 AA012610/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Notch; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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