Abnormal mechanosensing underlie aortic aneurysm formation
| Project/Area Number |
18K15057
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Yamashiro Yoshito 筑波大学, 生存ダイナミクス研究センター, 助教 (70751923)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 大動脈瘤 / シグナル伝達 / メカノトランスダクション / 細胞外マトリクス / Thrombospondin-1 / YAP / 細胞接着斑 / PAR-1 / メカノセンシング / 血管生物 |
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| Outline of Final Research Achievements |
Thoracic aortic aneurysms (TAAs) are life-threatening diseases defined as a permanent abnormal dilatation of the thoracic aorta. Abnormal mechanosensing of smooth muscle cells (SMCs) has been suggested to drive the formation of TAAs, however, the precise molecular mechanism has not been elucidated. We found that the matricellular protein, Thrombospondin-1 (Thbs1) , was highly upregulated in TAAs of human and mouse. Deletion of Thbs1 in aneurysm mice prevented the aneurysm formation. In addition, mechanical stretch-induced Thbs1 regulated nuclear translocation of Yes-associated protein (YAP). We thus proposed a mechanism of Thbs1-mediated mechanotransduction, may serve a potential therapeutic target for treating TAAs.
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| Academic Significance and Societal Importance of the Research Achievements |
大動脈瘤は内科的治療法が確立されておらず、その開発のためには標的分子を明らかにすることが重要である。本研究では、血管のメカニカルストレス応答を担う細胞外マトリクスの役割と、大動脈瘤発生の分子メカニズムを明らかにすることを目的とし、Thbs1がメカニカルストレス応答を担うこと、大動脈瘤発症に関与することを明らかにした。今後、本研究を基盤として大動脈瘤の新しい治療法開発が期待できる。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Role of thrombospondin-1 in mechanotransduction and development of thoracic aortic aneurysm in mouse and humans.2018
Author(s)
Yamashiro Y, Thang BQ, Shin SJ, Lino CA, Nakamura T, Kim J, Sugiyama K, Tokunaga C, Sakamoto H, Osaka M, Davis EC, Wagenseil JE, Hiramatsu Y and Yanagisawa H.
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Journal Title
Circulation Research
Volume: 123(6)
Issue: 6
Pages: 660-672
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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