Platelet-derived growth factor-specific regulation of the MCP-1 promoter in rat aortic smooth muscle cells.
Item
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Title
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Platelet-derived growth factor-specific regulation of the MCP-1 promoter in rat aortic smooth muscle cells.
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Identifier
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AAI9917632
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identifier
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9917632
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Creator
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Bogdanov, Vladimir Y.
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Contributor
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Adviser: Mark B. Taubman
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Cell | Biology, Genetics | Biology, Molecular
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Abstract
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Monocyte chemoattractant protein-1 (MCP-1) is a member of the family of "immediate early" genes induced by growth factors and cytokines in a variety of cell types. MCP-1 encodes a low molecular weight secretory glycoprotein that is a member of the C-C subfamily of chemokines. MCP-1 is thought to play an important role in inflammation and in the recruitment of monocytes/macrophages to the vessel wall during the development of atherosclerosis and in vessel reocclusion following percutaneous transluminal coronary angioplasty (PTCA). Taubman et al. (1992) have previously reported that the induction of MCP-1 in rat aortic vascular smooth muscle cells (VSMC) was specific for platelet-derived growth factor (PDGF) and was not seen with other growth agonists, including angiotensin II. This thesis describes the identification of a region in the proximal rat MCP-1 promoter that is responsive to PDGF but not to other growth factors (angiotensin II and alpha-thrombin) or cytokines (interleukin 1beta and tumor necrosis factor-alpha). Transient transfection assays of rat VSMC with promoter constructs containing the luciferase reporter gene were the main experimental approaches used to identify the PDGF-responsive promoter region. The full response to PDGF (approximately 6 fold) requires the cooperative activity of two potentially novel cis-acting elements, at positions -146 to 128 and -84 to -59 of the published genomic sequence. These two elements produce different patterns in electrophoretic mobility shift assays. Nevertheless, they appear to bind the same PDGF-responsive protein species. Further analysis of these elements and trans-acting factors that interact with them should provide important insights into PDGF-specific responses in VSMC and may assist in developing new therapeutic approaches to highly selective inhibition of gene expression in the vessel wall.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
