| Project/Area Number |
18K07011
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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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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Akita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
前田 大地 大阪大学, 医学系研究科, 特任教授(常勤) (30585500)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 心不全 / 網羅的遺伝子発現解析 / RNA-seq / バイオマーカー / 心筋細胞 / 拡張型心筋症 / 遺伝子解析 / 心不全バイオマーカー / RNAシークエンス / 病理解剖 / 凍結心筋 / 網羅的遺伝子解析 / 心臓凍結標本 / マイクロRNAマイクロアレイ |
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| Outline of Final Research Achievements |
In this study, RNA-seq analysis was performed on 12 autopsy hearts including Control. From the comparison between the heart failure group and the control group, a total of 6286 genes whose expression were up-regulated or down-regulated were confirmed. Among them, genes encoding proteins found in heart failure such as ANP and CRP were confirmed. From this result, it was considered that the selected autopsy heart was consistent with the heart failure cases. Some genes were picked up, and verified by RT-PCR. The gene expression were confirmed same as the results of RNA-seq analysis. Among them, it was found that three catalytic subunits of NADPH oxidase, NOX1-5 and DUOX1, 2, were up-regulated. Currently, we are investigating the correlation between the NOX1 gene expression and the ejection fraction of the left ventricle, which is an index of heart failure.
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| Academic Significance and Societal Importance of the Research Achievements |
世界全体で心不全に罹患している患者は多く、心不全治療は現在でも臨床現場におけるトピックの一つである。心不全の病態解明、治療への応用のためには心不全時心筋の分子生物学的解析が必要とされるが、心臓はその特殊性から網羅的遺伝子解析による知見の蓄積が非常に乏しい。本研究では心不全症例の剖検心で網羅的遺伝子発現解析を行い、心不全患者の心筋における遺伝子発現を明らかとした。その中から新規の心不全指標となりうる遺伝子が同定された。新たな心不全の指標となりうるかについてはさらなる解析が必要だが、心不全を早期で捉え、早期治療介入や治療ターゲット、創薬への応用として期待され、その社会的意義は大きいと考えられる。
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