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Redox-Sensitive Transcription Factor Nrf2 Regulates Vascular Smooth Muscle Cell Migration and Neointimal Hyperplasia

Redox-Sensitive Transcription Factor Nrf2 Regulates Vascular Smooth Muscle Cell Migration and... Redox-Sensitive Transcription Factor Nrf2 Regulates Vascular Smooth Muscle Cell Migration and Neointimal Hyperplasia Takashi Ashino, Masayuki Yamamoto, Takemi Yoshida, Satoshi Numazawa Objective—Reactive oxygen species are important mediators for platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells, whereas excess reactive oxygen species–induced oxidative stress contributes to the development and progression of vascular diseases, such as atherosclerosis. Activation of the redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), is pivotal in cellular defense against oxidative stress by transcriptional upregulation of antioxidant proteins. This study aimed to elucidate the role of Nrf2 in PDGF-mediated vascular smooth muscle cell migration and neointimal hyperplasia. Approach and Results—PDGF promoted nuclear translocation of Nrf2, followed by the induction of target genes, including NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, and thioredoxin-1. Nrf2 depletion by small interfering RNA enhanced PDGF-promoted Rac1 activation and reactive oxygen species production and persistently phosphorylated downstream extracellular signal–regulated kinase-1/2. Nrf2 depletion enhanced vascular smooth muscle cell migration in response to PDGF and wound scratch. In vivo, Nrf2-deficient mice showed enhanced neointimal hyperplasia in a wire injury model. Conclusion—These findings suggest that the Nrf2 system is important for PDGF-stimulated vascular smooth muscle cell migration by regulating reactive oxygen species elimination, which may http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Redox-Sensitive Transcription Factor Nrf2 Regulates Vascular Smooth Muscle Cell Migration and Neointimal Hyperplasia

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References (46)

Copyright
© 2013 American Heart Association, Inc.
ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/ATVBAHA.112.300614
pmid
23413426
Publisher site
See Article on Publisher Site

Abstract

Redox-Sensitive Transcription Factor Nrf2 Regulates Vascular Smooth Muscle Cell Migration and Neointimal Hyperplasia Takashi Ashino, Masayuki Yamamoto, Takemi Yoshida, Satoshi Numazawa Objective—Reactive oxygen species are important mediators for platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells, whereas excess reactive oxygen species–induced oxidative stress contributes to the development and progression of vascular diseases, such as atherosclerosis. Activation of the redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), is pivotal in cellular defense against oxidative stress by transcriptional upregulation of antioxidant proteins. This study aimed to elucidate the role of Nrf2 in PDGF-mediated vascular smooth muscle cell migration and neointimal hyperplasia. Approach and Results—PDGF promoted nuclear translocation of Nrf2, followed by the induction of target genes, including NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, and thioredoxin-1. Nrf2 depletion by small interfering RNA enhanced PDGF-promoted Rac1 activation and reactive oxygen species production and persistently phosphorylated downstream extracellular signal–regulated kinase-1/2. Nrf2 depletion enhanced vascular smooth muscle cell migration in response to PDGF and wound scratch. In vivo, Nrf2-deficient mice showed enhanced neointimal hyperplasia in a wire injury model. Conclusion—These findings suggest that the Nrf2 system is important for PDGF-stimulated vascular smooth muscle cell migration by regulating reactive oxygen species elimination, which may

Journal

Arteriosclerosis, Thrombosis, and Vascular BiologyWolters Kluwer Health

Published: Apr 1, 2013

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