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A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages
Increasing evidence suggests that the cytokine transforming growth factor-β (TGF-β) inhibits the development of atherosclerosis. The lipoprotein lipase (LPL) enzyme expressed by macrophages has been implicated in the pathogenesis of atherosclerosis by stimulating the uptake of lipoprotein particles....
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1062872/ https://www.ncbi.nlm.nih.gov/pubmed/15755745 http://dx.doi.org/10.1093/nar/gki280 |
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author | Irvine, Scott A. Foka, Pelagia Rogers, Sarah A. Mead, James R. Ramji, Dipak P. |
author_facet | Irvine, Scott A. Foka, Pelagia Rogers, Sarah A. Mead, James R. Ramji, Dipak P. |
author_sort | Irvine, Scott A. |
collection | PubMed |
description | Increasing evidence suggests that the cytokine transforming growth factor-β (TGF-β) inhibits the development of atherosclerosis. The lipoprotein lipase (LPL) enzyme expressed by macrophages has been implicated in the pathogenesis of atherosclerosis by stimulating the uptake of lipoprotein particles. Unfortunately, the action of TGF-β on the expression of LPL in macrophages remains largely unclear. We show that TGF-β inhibits LPL gene expression at the transcriptional level. Transient transfection assays reveal that the −31/+187 sequence contains the minimal TGF-β-responsive elements. Electrophoretic mobility shift assays show that Sp1 and Sp3 interact with two regions in the −31/+187 sequence. Mutations of these Sp1/Sp3 sites abolish the TGF-β-mediated suppression whereas multimers of the sequence impart the response to a heterologous promoter. TGF-β has no effect on the binding or steady-state polypeptide levels of Sp1 and Sp3. These results, therefore, suggest a novel mechanism for the TGF-β-mediated repression of LPL gene transcription that involves regulation of the action of Sp1 and Sp3. |
format | Text |
id | pubmed-1062872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-10628722005-03-08 A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages Irvine, Scott A. Foka, Pelagia Rogers, Sarah A. Mead, James R. Ramji, Dipak P. Nucleic Acids Res Article Increasing evidence suggests that the cytokine transforming growth factor-β (TGF-β) inhibits the development of atherosclerosis. The lipoprotein lipase (LPL) enzyme expressed by macrophages has been implicated in the pathogenesis of atherosclerosis by stimulating the uptake of lipoprotein particles. Unfortunately, the action of TGF-β on the expression of LPL in macrophages remains largely unclear. We show that TGF-β inhibits LPL gene expression at the transcriptional level. Transient transfection assays reveal that the −31/+187 sequence contains the minimal TGF-β-responsive elements. Electrophoretic mobility shift assays show that Sp1 and Sp3 interact with two regions in the −31/+187 sequence. Mutations of these Sp1/Sp3 sites abolish the TGF-β-mediated suppression whereas multimers of the sequence impart the response to a heterologous promoter. TGF-β has no effect on the binding or steady-state polypeptide levels of Sp1 and Sp3. These results, therefore, suggest a novel mechanism for the TGF-β-mediated repression of LPL gene transcription that involves regulation of the action of Sp1 and Sp3. Oxford University Press 2005 2005-03-08 /pmc/articles/PMC1062872/ /pubmed/15755745 http://dx.doi.org/10.1093/nar/gki280 Text en © The Author 2005. Published by Oxford University Press. All rights reserved |
spellingShingle | Article Irvine, Scott A. Foka, Pelagia Rogers, Sarah A. Mead, James R. Ramji, Dipak P. A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages |
title | A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages |
title_full | A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages |
title_fullStr | A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages |
title_full_unstemmed | A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages |
title_short | A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages |
title_sort | critical role for the sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1062872/ https://www.ncbi.nlm.nih.gov/pubmed/15755745 http://dx.doi.org/10.1093/nar/gki280 |
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