Identification of master regulator of osteoblast differentiation in valve calcification
| Project/Area Number |
19H03740
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 55030:Cardiovascular surgery-related
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| Research Institution | Ehime University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂上 倫久 愛媛大学, 医学系研究科, 講師(特定教員) (20709266)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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| Keywords | 大動脈弁狭窄症 / 石灰化 / 骨芽細胞 / 弁膜症 / AS / 弁間質細胞 / 大動脈弁 / 間質細胞 / トランスレーショナルリサーチ / 心血管 |
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| Outline of Research at the Start |
これまで我々は、網羅的遺伝子発現解析により石灰化大動脈弁由来の間質細胞に、特異的に高発現する遺伝子群を同定している。これらの遺伝子群は、弁間葉系幹細胞を骨芽細胞に分化させた際にも発現上昇することから、骨芽細胞への分化に必須である可能性が高い。本研究では、これらの遺伝子群を対象に、in vivoおよびin vitroでの機能解析を実施する。また、その分子機能阻害剤を探索することにより、新規大動脈弁狭窄症治療薬としてのリード化合物の導出を目指す。
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| Outline of Final Research Achievements |
There is currently no pharmacological treatment for aortic valve stenosis (AS), and the molecular mechanisms underlying calcification of the aortic valve remain unknown. In this study, we aimed to identify the differentiation mechanism from undifferentiated interstitial cells to osteoblasts and focus on tissue calcification in the pathogenesis of AS. We also aimed to identify proteins that regulate aortic valve calcification and develop inhibitors for their function. We successfully identified 12 master regulatory genes involved in osteoblast differentiation, including Notch signaling ligands. Additionally, we discovered secreted proteins that are downregulated in the vicinity of calcified tissues during the progression of AS, raising expectations for the development of novel preventive and therapeutic drugs for AS.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦における弁膜症の罹患率は年々増加傾向にあり、外科的治療法の発展のみならず新たな薬物治療法の開発は急務である。本研究は大動脈弁狭窄症の中でも特にその重症度と関連する大動脈弁石灰化の分子メカニズム解明に焦点を当てたものである。試験管内で実施した石灰化アッセイを用いて特定した１２種類の大動脈弁石灰化関連分子は、今後大動脈弁石灰化を予防または治療する薬剤の開発に応用できる可能性がある。
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] Valve Interstitial Cell-Specific Cyclooxygenase-1 Associated With Calcification of Aortic Valves.2019
Author(s)
Sakaue T, Hamaguchi M, Aono J, Nakashiro KI, Shikata F, Kawakami N, Oshima Y, Kurata M,?Nanba D, Masumoto J, Yamaguchi O, Higashiyama S, Izutani H.
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Journal Title
Ann Thorac Surg
Volume: S0003-4975
Issue: 1
Pages: 31717-5
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Valve Interstitial Cell-Specific Cyclooxygenase-1 Associated With Calcification of Aortic Valves.2019
Author(s)
Sakaue T, Hamaguchi M, Aono J, Nakashiro KI, Shikata F, Kawakami N, Oshima Y, Kurata M, Nanba D, Masumoto J, Yamaguchi O, Higashiyama S, Izutani H.
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Journal Title
Ann Thorac Surg.
Volume: 19
Pages: 31717-5
Related Report
Peer Reviewed
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