A role of T-box genes in development of cardiovascular diseases
Project/Area Number |
16H05359
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Keio University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
土橋 隆俊 慶應義塾大学, 医学部(信濃町), 共同研究員 (10286528)
内田 敬子 慶應義塾大学, 保健管理センター(日吉), 講師 (50286522)
湯浅 慎介 慶應義塾大学, 医学部(信濃町), 講師 (90398628)
家田 真樹 慶應義塾大学, 医学部, 助教 (70296557)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 発生・分化 / 遺伝子 / 循環器 / 発現制御 / シグナル伝達 / 循環器・高血圧 |
Outline of Final Research Achievements |
Utilizing the murine model of 22q11.2 deletion syndrome (Tbx1 hypomorphic mouse), we clarified that the phenotype of congenital heart disease, or truncus arteriosus, became milder by administration of folate to the pregnant female mice. Folate rescued abnormal development of neural crest derived mesenchymal cells that give rise to the outflow tract septum. The expression of numerous regulatory factors for cardiac development and neural crest migration and differentiation were altered by folate administration. We also identified that Tbx4 played a role in maintenance of undifferentiated mesenchymal cells in the lungs by directly regulating Fgf10, a soluble growth factor essential for the lung development. Finally, we established Tbx20 knock out mouse lines using CRISPR/Cas9 system to test the genetic interaction between Tbx20 and Tbx1 during development of the heart.
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Academic Significance and Societal Importance of the Research Achievements |
本研究の結果として、多因子遺伝の先天性心血管疾患の成因解明に対して新たなアプローチが確立する。今後、複雑な先天性心血管疾患に対する新たな治療戦略として、幹細胞による再生医療の応用が期待されており、このような成果による個々の先天性心血管疾患の成因解明の蓄積は、オーダーメード医療のための基礎的知見として重要である。ヒト染色体・遺伝子異常症の染色体や遺伝子そのものを治療・修復する医療は困難だが、本研究によるTbx1発現低下マウスの心血管疾患の表現型の軽症化する環境・epigenetic因子またはその分子経路の特定は、将来22q11.2欠失症候群の心疾患を軽症化する治療法の実現につながる可能性がある。
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Report
(4 results)
Research Products
(55 results)
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[Journal Article] Mode of death and predictors of mortality in adult Fontan survivors: A Japanese multicenter observational study.2019
Author(s)
Ohuchi H, Inai K, Nakamura M, Park IS, Watanabe M, Hiroshi O, Kim KS, Sakazaki H, Waki K, Yamagishi H, Yamamura K, Kuraishi K, Miura M, Nakai M, Nishimura K, Niwa K; JSACHD Fontan Investigators
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Journal Title
Int J Cardiol
Volume: 276
Pages: 74-80
DOI
Related Report
Peer Reviewed
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[Journal Article] Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study.2018
Author(s)
Miyata K, Kaneko T, Morikawa Y, Sakakibara H, Matsushima T, Misawa M, Takahashi T, Nakazawa M, Tamame T, Tsuchihashi T, Yamashita Y, Obonai T, Chiga M, Hori N, Komiyama O, Yamagishi H, Miura M; Post RAISE group.
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Journal Title
Lancet Child Adolesc Health
Volume: 2
Pages: 855-862
DOI
Related Report
Peer Reviewed
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[Journal Article] Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction.2018
Author(s)
Miyamoto K, Akiyama M, Tamura F, Isomi M, Yamakawa H, Sadahiro T, Muraoka N, Kojima H, Haginiwa S, Kurotsu S, Tani H, Wang L, Qian L, Inoue M, Ide Y, Kurokawa J, Yamamoto T, Seki T, Aeba R, Yamagishi H, Fukuda K, Ieda M.
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Journal Title
Cell Stem Cell.
Volume: 22
Pages: 91-103
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events.2018
Author(s)
Miura M, Kobayashi T, Kaneko T, Ayusawa M, Fukazawa R, Fukushima N, Fuse S, Hamaoka K, Hirono K, Kato T, Mitani Y, Sato S, Shimoyama S, Shiono J, Suda K, Suzuki H, Maeda J, Waki K; and The Z-score Project 2nd Stage Study Group, Kato H, Saji T, Yamagishi H, et al.
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Journal Title
JAMA Pediatr.
Volume: 5
Pages: e180030
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 胎児臨床心臓発生学2016
Author(s)
山岸敬幸
Organizer
第18回日本イアンドナルド超音波講座
Place of Presentation
都市センターホテル(東京都千代田区)
Year and Date
2016-11-27
Related Report
Invited
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[Presentation] 先天性心疾患の疫学と遺伝診療2016
Author(s)
山岸敬幸
Organizer
第6回広島キッズハート&ラングフォーラム
Place of Presentation
広島インテリジェントホテル(広島県広島市)
Year and Date
2016-11-25
Related Report
Invited
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[Presentation] 遺伝性心疾患の診断と管理2016
Author(s)
山岸敬幸
Organizer
第14回成人先天性心疾患セミナー
Place of Presentation
聖路加国際病院(東京都中央区)
Year and Date
2016-06-26
Related Report
Invited
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