| Project/Area Number |
15K08239
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
IWATA KAZUMI 京都府立医科大学, 医学(系)研究科(研究院), 講師 (60305571)
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| Co-Investigator(Kenkyū-buntansha) |
松本 みさき 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80533926)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 心線維化 / 活性酸素種 / 心線維芽細胞 / 心筋細胞 / ゲノム編集 / NADPHオキシダーゼ / 遺伝子組換えマウス |
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| Outline of Final Research Achievements |
In this study, we demonstrated a novel role for NOX1, a non-phagocytic isoform of superoxide-producing NADPH oxidase, in cardiac fibrosis following drug-induced myocardial injury. A single-dose administration of doxorubicin (DOX) caused severe cardiac fibrosis in wild-type mice, but it was significantly attenuated in Nox1-deficient mice. When H9c2 cardiomyocytes were exposed to their homogenate, a dose-dependent increase in NOX1 mRNA was observed. When isolated cardiac fibroblasts were exposed to H9c2 homogenates, increased proliferation and up-regulation of collagen 3a1 mRNA were demonstrated. These changes were significantly attenuated in cardiac fibroblasts exposed to homogenates from H9c2 harboring disrupted Nox1. These findings suggest that up-regulation of NOX1 following cellular damage promotes cardiac fibrosis by aggravating the pro-fibrotic response of cardiac fibroblasts.
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