the role of cellular senescence on the pathogenesis of acute aortic dissection
| Project/Area Number |
16K10668
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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 surgery
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
槇野 香奈子 慶應義塾大学, 医学部(信濃町), 助教 (10772402)
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| Project Period (FY) |
2016-04-01 – 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 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 細胞老化 / 大動脈解離 / 血管 / p16 / p21 / p53 / 炎症 / 子宮 |
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| Outline of Final Research Achievements |
Acute aortic dissection(AAD) is a critical acute vascular disease with high mortality rate, but its pathogenesis remains unknown. We established a novel mouse model and we found the upregulation of representative senescence markers and the secretion of pro-inflammatory cytokines together with JAK2 phosphorylation coinciding senescence-associated secretory phenotype. We tested AAD incidence using senescence key molecule deleted mice, senolytics treated mice, and JAK inhibitor treated mice. All the mice showed significant decrease in AAD incidence, especially p21 knockout mice. P21-mediated senescence and the following JAK signaling might be involved in the pathogenesis of AAD.
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| Academic Significance and Societal Importance of the Research Achievements |
急性大動脈解離(AAD)は致死率の高い循環器救急疾患であるが、発症機序の研究が進んでおらず、治療も外科的治療が主体である。我々の研究により発症に係る鍵因子とシグナル経路が明らかになり、マウスモデルでは既に別用途で臨床使用されている薬剤も解離発症抑制に効果的であることが示された。将来的にこは、p21をターゲットとした遺伝子治療やJAK阻害剤、細胞老化阻害剤を用いた大動脈解離の薬物治療に臨床応用するところまで発展させられる可能性があり、本研究の社会的意義は大きいと考えられる。
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Report
(5 results)
Research Products
(7 results)
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[Journal Article] F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus.2017
Author(s)
Egashira M, Hirota Y, Shimizu-Hirota R, Saito-Fujita T, Haraguchi H, Matsumoto L, Matsuo M, Hiraoka T, Tanaka T, Akaeda S, Takehisa C, Saito-Kanatani M, Maeda K, Fujii T, Osuga Y.
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Journal Title
Endocrinology
Volume: 印刷中
Issue: 7
Pages: 2344-2353
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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