| Project/Area Number |
17K10153
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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 |
Pediatrics
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| Research Institution | Keio University |
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Principal Investigator |
Uchida Keiko 慶應義塾大学, 保健管理センター(日吉), 准教授 (50286522)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肺動脈 / 転写因子 / 平滑筋 / 肺動脈性肺高血圧症 / 発生 / 肺血管 |
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| Outline of Final Research Achievements |
One of the transcription factors which are crucial for organogenesis, Tbx4, is highly expressed in the lung mesenchyme. Lung mesenchyme consists of undifferentiated progenitor cells, which give rise to various cell types, possibly including pulmonary vascular cells. Recently TBX4 mutations have reported in patients with PAH. However, the mechanisms of pulmonary vascular development and pathogenesis of pulmonary arterial hypertension (PAH) remain unclear.
We found that Tbx4 knockdown in lung mesenchymal cells facilitated tube formation activity, which is characteristic of endothelial cells, and that Tbx4 knockdown in lung organ culture inhibited lung development. Our results suggest that Tbx4 in undifferentiated mesenchymal progenitor cells may be involved in the formation of both airways and vessels in the lungs. The roles of Tbx4 in the lung mesenchyme may pave the way for novel mechanisms underlying pulmonary vascular development and pathogenesis of PAH.
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| Academic Significance and Societal Importance of the Research Achievements |
肺血管は体血管とは異なる性質を持ち、生命に必須であるガス交換に重要な役割を担う。また、肺動脈性肺高血圧症は近年治療薬が複数開発されたが未だに肺移植を要する難治性の疾患である。本研究では、Tbx4という胎生期の肺血管前駆細胞を含むと考えられている肺間葉系細胞に発現する転写因子に着目し、肺血管発生ならびに肺動脈性肺高血圧症発症の分子機構の一端となる知見を得た。本研究の成果は肺血管再生医療や肺動脈性肺高血圧症の新規治療標的の開発に貢献しうる。
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