Application of genome editing and development-associated APJ ligand for exploring novel therapeutic candidates for heart failure
| Project/Area Number |
15K15304
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Akita University |
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Principal Investigator |
Keiji Kuba 秋田大学, 医学(系)研究科(研究院), 教授 (10451915)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ELABELA / Apelin / CRISPR/Cas9 / heart failure / ACE2 / FoxM1 / ゲノム編集 / Elabela / CRISPR |
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| Outline of Final Research Achievements |
We investigated the role of APJ ligand ELABELA and novel heart failure gene candidates in controlling heart functions by utilizing CRISPR/Cas9 genome editing in ES cells and functional analyses of G0 mice. ELA peptide treatment improved heart function and hypertrophy and reduced cardiac fibrosis in mice with TAC pressure overload. Mechanistically, ELA down-regulated transcription of ACE and thereby negatively regulates renin-angiotensin system. We also generated several new lines of mutant G0 mice for heart failure gene candidates and analyzed heart functions. Furthermore, we crossed the G0 mice for F1 and F2 generations and analyzed heart functions, leading to confirmation of 5 heart failure genes. The candidate approach with rapid generation and functional screening is efficient and useful in identifying novel heart failure genes and might contribute to boosting up cardiovascular research.
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage2017
Author(s)
Sato T, Sato C, Kadowaki A, Watanabe H, Ho L, Ishida J, Yamaguchi T, Kimura A, Fukamizu A, Penninger JM, Reversade B, Ito H, Imai Y, Kuba K
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Journal Title
Cardiovasc Res
Volume: 113(7)
Issue: 7
Pages: 760-769
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy.2017
Author(s)
Kimura H, Eguchi S, Sasaki J, Kuba K, Nakanishi H, Takasuga S, Yamazaki M, Goto A, Watanabe H, Itoh H, Imai Y, Suzuki A, Mizushima N, Sasaki T
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Journal Title
JCI Insight
Volume: 2
Issue: 1
Pages: 89462-89478
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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