The role of selective autophagy for the degradation of inflammasome in the progression of heart failure
| Project/Area Number |
17K09570
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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 |
Cardiovascular medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Yasuhiro Maejima 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (40401393)
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| Co-Investigator(Kenkyū-buntansha) |
小西 正則 東京医科歯科大学, 医学部附属病院, 助教 (70792018)
磯部 光章 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (80176263)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 心不全 / インフラマソーム / オートファジー |
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| Outline of Final Research Achievements |
The aim of this study is to establish a novel target of heart failure therapy by elucidating the role of selective autophagy that degrade inflammasome in the hearts. We found that suppression of autophagy machinery enhances accumulation of inflammasome in cardiomyocytes, thereby abrogating cardiac function in response to pressure overload in the hearts of the mice. We also demonstrated that there is the physically interaction between TRIM20 and NLRP3. In addition, we have shown that knockdown of TRIM20 enhances inflammasome activity in cardiomyocytes by suppressing selective autophagy for the degradation of inflammasome. Thus, we concluded that selective autophagy for the degradation of inflammasome would be a possible target for establishing novel therapeutic strategy against heart failure.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の申請研究では、培養心筋細胞を用いたin vitro実験ならびに実験的心筋梗塞モデルを用いて、心不全の病態において微細なタンパク複合体を特異的に分解する選択的オートファジーが関与しているのかどうかと、この選択的オートファジーの制御系が心不全の病態ではどのような影響を受けるのかについて明らかにした。特に、インフラマソームを特異的に分解する選択的オートファジーの分子機序を明らかにし、このメカニズムの破綻がインフラマソームの機能亢進を惹起して心不全の病態を悪化させているのかどうかを明らかにし、新規の心不全治療法の開発につながるような知見を見いだせた点に意義があると考える。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia.2019
Author(s)
Saito T, Nah J, Oka SI, Mukai R, Monden Y, Maejima Y, Ikeda Yoshiyuki, Sciarretta S, Liu T, Li H, Baljinnyam E, Fraidenraich D, Fritzky L, Zhai P, Ichinose S, Isobe M, Hsu CP, Kundu M, Sadoshima J.
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Journal Title
Journal of Clinical Investigation
Volume: 129
Issue: 2
Pages: 802-819
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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