| Fluid shear stress-induced transcriptional activation of the vascular endothelial growth factor receptor-2 gene requires Sp1-dependent DNA binding. | |
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MedLine Citation:
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PMID: 12560084 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hemodynamic forces play a fundamental role in the regulation of endothelial cell survival. As signaling via the vascular endothelial growth factor (VEGF) receptor-2 pathway has been previously demonstrated to impact endothelial cell survival, we hypothesized that laminar shear stress may facilitate survival in part by inducing VEGF receptor-2 expression. This study shows a time- and dose-dependent upregulation of endothelial VEGF receptor-2 expression by fluid shear stress in microvascular and large-vessel derived endothelial cells. A functional analysis of the 5'-regulatory region of the VEGF receptor-2 promoter localized the shear stress-response element to a sequence between bp -60 and -37 that encompasses two adjacent consensus Sp1 transcription factor binding sites. Constitutive and shear stress-inducible Sp1-dependent complexes are bound to this element, indicating that fluid shear stress-induced transcriptional activation of the VEGF receptor-2 gene requires Sp1-dependent DNA binding. Together, these results suggest that biomechanical stimulation may lead to endothelial cell survival by upregulating VEGF receptor-2 expression. |
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Authors:
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Carmen Urbich; Monika Stein; Kerstin Reisinger; Roland Kaufmann; Stefanie Dimmeler; Jens Gille |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: FEBS letters Volume: 535 ISSN: 0014-5793 ISO Abbreviation: FEBS Lett. Publication Date: 2003 Jan |
Date Detail:
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Created Date: 2003-01-31 Completed Date: 2003-03-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0155157 Medline TA: FEBS Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 87-93 Citation Subset: IM |
Affiliation:
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Molecular Cardiology, Department of Internal Medicine IV, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Cells, Cultured DNA / metabolism* Electrophoretic Mobility Shift Assay Endothelium, Vascular / cytology, metabolism* Humans RNA, Messenger / metabolism Regulatory Sequences, Nucleic Acid / physiology Response Elements / physiology Sp1 Transcription Factor / metabolism* Stress, Mechanical Transcriptional Activation / physiology* Up-Regulation / physiology Vascular Endothelial Growth Factor Receptor-2 / genetics*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Sp1 Transcription Factor; 9007-49-2/DNA; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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