| Project/Area Number |
25860670
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OI Katsuyuki 東京医科歯科大学, 医学部, 非常勤講師 (50633765)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | WNKシグナル / 血管平滑筋 / 塩分感受性 / 高血圧 / WNK / トランスポーター / WNK3 / NKCC1 / アンギオテンシンII |
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| Outline of Final Research Achievements |
At first, we identified the WNK3-OSR1/SPAK-NKCC1 cascade in vascular smooth muscle cells and found that it constitutes an important mechanism of vascular constriction by angiotensin II (AngII). Recently, the kelch-like protein 3 (KLHL3)/Cullin3 complex was identified as an E3 ubiquitin ligase for with no lysine (WNK) kinases. Therefore, we investigated the involvement of KLHL proteins in AngII-induced WNK3 activation of vascular smooth muscle cells. In the mouse aorta, KLHL3 was not expressed, but KLHL2, the closest homolog of KLHL3, was expressed. Salt depletion and acute infusion of AngII decreased KLHL2 and increased WNK3 levels in the mouse aorta. The AngII-induced decrease in KLHL2 was caused by increased autophagy-mediated degradation. Thus, we identified a novel component of signal transduction in AngII-induced vascular contraction that could be a promising drug target.
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