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NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II
The vasoactive peptide urotensin-II (U-II) has been associated with vascular remodeling in different cardiovascular disorders. Although U-II can induce reactive oxygen species (ROS) by the NADPH oxidase NOX4 and stimulate smooth muscle cell (SMC) proliferation, the precise mechanisms linking U-II to...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216667/ https://www.ncbi.nlm.nih.gov/pubmed/21965295 http://dx.doi.org/10.1091/mbc.E10-12-0971 |
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author | Diebold, Isabel Petry, Andreas Burger, Maximilian Hess, John Görlach, Agnes |
author_facet | Diebold, Isabel Petry, Andreas Burger, Maximilian Hess, John Görlach, Agnes |
author_sort | Diebold, Isabel |
collection | PubMed |
description | The vasoactive peptide urotensin-II (U-II) has been associated with vascular remodeling in different cardiovascular disorders. Although U-II can induce reactive oxygen species (ROS) by the NADPH oxidase NOX4 and stimulate smooth muscle cell (SMC) proliferation, the precise mechanisms linking U-II to vascular remodeling processes remain unclear. Forkhead Box O (FoxO) transcription factors have been associated with redox signaling and control of proliferation and apoptosis. We thus hypothesized that FoxOs are involved in the SMC response toward U-II and NOX4. We found that U-II and NOX4 stimulated FoxO activity and identified matrix metalloproteinase-2 (MMP2) as target gene of FoxO3a. FoxO3a activation by U-II was preceded by NOX4-dependent phosphorylation of c-Jun NH(2)-terminal kinase and 14-3-3 and decreased interaction of FoxO3a with its inhibitor 14-3-3, allowing MMP2 transcription. Functional studies in FoxO3a-depleted SMCs and in FoxO3a(–/–) mice showed that FoxO3a was important for basal and U-II–stimulated proliferation and vascular outgrowth, whereas treatment with an MMP2 inhibitor blocked these responses. Our study identified U-II and NOX4 as new activators of FoxO3a, and MMP2 as a novel target gene of FoxO3a, and showed that activation of FoxO3a by this pathway promotes vascular growth. FoxO3a may thus contribute to progression of cardiovascular diseases associated with vascular remodeling. |
format | Online Article Text |
id | pubmed-3216667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32166672012-01-30 NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II Diebold, Isabel Petry, Andreas Burger, Maximilian Hess, John Görlach, Agnes Mol Biol Cell Articles The vasoactive peptide urotensin-II (U-II) has been associated with vascular remodeling in different cardiovascular disorders. Although U-II can induce reactive oxygen species (ROS) by the NADPH oxidase NOX4 and stimulate smooth muscle cell (SMC) proliferation, the precise mechanisms linking U-II to vascular remodeling processes remain unclear. Forkhead Box O (FoxO) transcription factors have been associated with redox signaling and control of proliferation and apoptosis. We thus hypothesized that FoxOs are involved in the SMC response toward U-II and NOX4. We found that U-II and NOX4 stimulated FoxO activity and identified matrix metalloproteinase-2 (MMP2) as target gene of FoxO3a. FoxO3a activation by U-II was preceded by NOX4-dependent phosphorylation of c-Jun NH(2)-terminal kinase and 14-3-3 and decreased interaction of FoxO3a with its inhibitor 14-3-3, allowing MMP2 transcription. Functional studies in FoxO3a-depleted SMCs and in FoxO3a(–/–) mice showed that FoxO3a was important for basal and U-II–stimulated proliferation and vascular outgrowth, whereas treatment with an MMP2 inhibitor blocked these responses. Our study identified U-II and NOX4 as new activators of FoxO3a, and MMP2 as a novel target gene of FoxO3a, and showed that activation of FoxO3a by this pathway promotes vascular growth. FoxO3a may thus contribute to progression of cardiovascular diseases associated with vascular remodeling. The American Society for Cell Biology 2011-11-15 /pmc/articles/PMC3216667/ /pubmed/21965295 http://dx.doi.org/10.1091/mbc.E10-12-0971 Text en © 2011 Diebold et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Diebold, Isabel Petry, Andreas Burger, Maximilian Hess, John Görlach, Agnes NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II |
title | NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II |
title_full | NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II |
title_fullStr | NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II |
title_full_unstemmed | NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II |
title_short | NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II |
title_sort | nox4 mediates activation of foxo3a and matrix metalloproteinase-2 expression by urotensin-ii |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216667/ https://www.ncbi.nlm.nih.gov/pubmed/21965295 http://dx.doi.org/10.1091/mbc.E10-12-0971 |
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