Pathological mechanism of cardiac fibrosis via caveolae-related proteins in pressure-loaded heart failure
| Project/Area Number |
18K07046
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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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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Ogata Takehiro 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10402877)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 心臓線維化 / 心不全 / 線維芽細胞 / 心筋線維化 / 線維化 / カベオラ |
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| Outline of Final Research Achievements |
To investigate the involvement of Cavin-2 in cardiac fibrosis, we generated two types of mice: systemic Cavin-2 knockout mice and fibroblast-specific Cavin-2 knockout mice. No abnormalities were observed in the development and growth of these mice. However, in a mouse model of left ventricular pressure-overloaded heart failure due to transverse aortic constriction, Cavin-2 deletion in cardiac fibroblasts resulted in marked suppression of myocardial fibrosis and cardiac dysfunction. Cardiac fibroblasts differentiate into activated myofibroblasts and promote collagen production and deposition upon TGF-β1 stimulation. Cavin-2 deletion in mouse embryonic fibroblasts suppressed TGF-β1-induced differentiation into myofibroblasts and collagen production.
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| Academic Significance and Societal Importance of the Research Achievements |
心不全における心臓線維化は心機能に負の影響を及ぼす。線維化の制御は患者の予後改善に重要である。線維化を抑制するため、これまでにTGF-β1受容体の阻害薬を使った治療が提案されているが過度な線維化抑制による心破裂など負の影響が懸念されている。本研究でCavin-2をターゲットにした線維化制御は生理的役割を損なうことなく線維化を抑制できる可能性が示された。本研究結果は、カベオラ関連線維化シグナルの制御による心不全治療法のための基礎基盤の構築に貢献するもとの考える。
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Report
(4 results)
Research Products
(10 results)
