| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Reactive oxygen species (ROS) are important mediators for platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells (VSMCs), whereas excess ROS-induced oxidative stress contributes to the development of vascular diseases, such as atherosclerosis. Activation of Nrf2 system 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 VSMC migration and neointimal hyperplasia. PDGF promoted nuclear translocation of Nrf2, followed by the induction of target genes. Nrf2 depletion enhanced PDGF-promoted ROS production and -enhanced VSMC migration. In vivo, Nrf2-deficient mice showed enhanced neointimal hyperplasia in a wire injury model. These findings suggest that the Nrf2 system plays an important role in PDGF-stimulated VSMC migration via regulating ROS elimination, which may contributes to neointimal formation after vascular injury.
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