| Project/Area Number |
19209029
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGAI Ryozo The University of Tokyo, 医学部附属病院, 教授 (60207975)
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| Co-Investigator(Kenkyū-buntansha) |
MANABE Ichiro 東京大学, 医学部附属病院, 特任准教授 (70359628)
WATANABE Masafumi 東京大学, 医学部附属病院, 助教 (60360096)
前村 浩二 東京大学, 医学部附属病院, 助教 (90282649)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥47,580,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥10,980,000)
Fiscal Year 2009: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2008: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2007: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
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| Keywords | 心不全 / 心肥大 / メタボリックシンドローム / 転写因子 / 炎症 / 動脈硬化 / 肥満 / 免疫 / KLF5 / TLR |
|---|
| Research Abstract |
To elucidate pathogenic mechanisms underlying metabolic syndrome and cardiovascular diseases, we analyzed molecular control mechanisms of cellular stress response and gene transcription by cardiovascular, metabolic and immune systems. We focused on Toll-like receptor (TLR) signaling in metabolic stress response and Kruppel-like factor (KLF) family transcription factors in stress response and tissue remodeling in cardiovascular and metabolic tissues. We found that free fatty acids induce pathologies in both cardiovascular and metabolic systems. Moreover, we found that signaling mechanisms for ER stress, TLR, and reactive oxygen species play a role in the response to free fatty acids. We also showed that cardiac fibroblasts play a pivotal role in cardiac response to pressure overload by generating cardiac fibroblast-specific K1f5 knockout mice. Furthermore, we identified IGF-1 as an essential mediator produced by cardiac fibroblasts in the cardiac response to pressure overload. In metabolic systems, we found that KLF5 is also important for β cell dysfunction and the control of appetite.
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