| Project/Area Number |
17K09965
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Collagenous pathology/Allergology
|
|---|
| Research Institution | Tohoku Medical and Pharmaceutical University (2018-2021)
Tohoku University (2017) |
|---|
Principal Investigator |
Shirota Yuko 東北医科薬科大学, 医学部, 准教授 (20455819)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
石井 智徳 東北大学, 大学病院, 特任教授 (10282138)
藤井 博司 東北大学, 医学系研究科, 准教授 (30531321)
藤原 亨 東北大学, 大学病院, 講師 (60333796)
|
|---|
| Project Period (FY) |
2017-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | 肺動脈性肺高血圧症 / 転写因子GATA2 / 2型自然リンパ球 / 転写因子GATA3 |
|---|
| Outline of Final Research Achievements |
The transcription factor GATA2 is essential for the development of vascular endothelial cells and hematopoietic cells differentiation, and about 10% of patients with GATA2 deficiency develop pulmonary arterial hypertension (PAH), but the details are unknown. We investigated the mechanism of pulmonary arterial hypertension (PAH) induced by GATA2 mutation and the involvement of type 2 innate lymphocytes (ILC2).GATA2-KO mice were kept in a hypoxic environment to induce PAH, and GATA2-KO mice showed significant pulmonary artery remodeling and significant GATA3 expression in the spleen compared to control mice. GATA3 is essential for ILC2 differentiation and maintenance, but the low number of ILC2 cells made it difficult to investigate in details. In GATA2-GFP knock-in mice, GATA-2 was significantly expressed in pulmonary arterioles.
GATA2-KO mice showed pulmonary arteriolar remodeling, suggesting that it may be a factor in the pathogenesis of PAH.
|
| Academic Significance and Societal Importance of the Research Achievements |
転写因子GATA1は，造血系の発生・維持や，血管内皮西郷の性質維持に重要であることが知られている．ヒトGATA2欠損症において，肺高血圧症(PH)を認める症例があるが，その詳細は不明である．今回の研究では，GATA2欠損マウスにおけるPH発症機序を明らかにすることを目的とした．GATA2欠損マウスでは，肺細動脈のリモデリングが起きやすいことを確認し,これがPH発症の要因となる可能性を示唆した．さらに, GATA2欠損マウスでは，GATA3 の発現が上昇していた．GATA3はILC2分化と維持に不可欠であり，ILC2とPH発症の関連についても検討したが，ILC2細胞数が少なく検討に難渋した．
|
