Exploring the new mechanisms of pulmonary hypertension with Liver RNA sequencing
| Project/Area Number |
20K17137
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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 53020:Cardiology-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Asano Ryotaro 国立研究開発法人国立循環器病研究センター, 病院, 非常勤研究員 (60827004)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肺高血圧症 / 網羅的遺伝子発現 / RNAシークエンス |
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| Outline of Research at the Start |
肺動脈性高血圧症（PAH）は原因不明に肺動脈リモデリングを生じ、右心不全から死に至る難病である。腸管から吸収された物質が肝臓に輸送されない門脈結紮モデルでは肺高血圧症病態が大幅に改善することから、PAH病態において腸－肝－肺連関が重要であると仮説を立てた。そこで肝障害モデル動物への肺高血圧負荷やPAH患者検体を通じて、PAHの新規病態形成機序を探索する。
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| Outline of Final Research Achievements |
Pulmonary hypertension causes remodeling of the pulmonary arteries in association with a variety of background diseases, including genetics, collagen disease, congenital heart disease, and liver injury. The mechanism of pulmonary artery remodeling is still unknown, but it is likely that some common pathway of background disease is impaired to form the pulmonary hypertension pathology. The liver is the largest organ in the human body, that is closely linked to multiple organs, and it has been reported that it may also play an important role in pulmonary hypertension. In this study, through liver RNA sequencing analysis of animal models and comprehensive analysis of pulmonary hypertension patient samples, we found that the protective gene X in the liver plays an important role in pulmonary hypertension.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、肝臓は肺高血圧症の病態形成機構の中でも重要な役割を果たしていることが裏づけられた。特に遺伝子Xは、肝臓での代謝関連する、肺高血圧症の保護的遺伝子であることを見出した。これにより近年注目を集める門脈圧亢進に伴う肺高血圧症を中心として肺高血圧症全般の新たなバイオマーカーや治療法開発につながる可能性がある。
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension2021
Author(s)
Masaki T, Okazawa M, Asano R, Inagaki T, Ishibashi T, Yamagishi A, Umeki-Mizushima S, Nishimura M, Manabe Y, Ishibashi-Ueda H, Shirai M, Tsuchimochi H, Pearson JT, Kumanogoh A, Sakata Y, Ogo T, Kishimoto T, Nakaoka Y
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Journal Title
Proc Natl Acad Sci U S A
Volume: 118
Issue: 11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pathological and clinical effects of interleukin-6 on human myocarditis2021
Author(s)
Amioka Naofumi、Nakamura Kazufumi、Kimura Tomonari、Ohta-Ogo Keiko、Tanaka Takehiro、Toji Tomohiro、Akagi Satoshi、Nakagawa Koji、Toh Norihisa、Yoshida Masashi、Miyoshi Toru、Nishii Nobuhiro、Watanabe Atsuyuki、Asano Ryotaro、Ogo Takeshi、Nakaoka Yoshikazu、Morita Hiroshi、Yanai Hiroyuki、Ito Hiroshi
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Journal Title
Journal of Cardiology
Volume: 78
Issue: 2
Pages: 157-165
DOI
Related Report
Peer Reviewed / Open Access
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