New mechanisms of perinatal cardiovascular regulation by class II PI3K
| Project/Area Number |
18K15010
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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 48020:Physiology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
Aki Sho 金沢大学, 医学系, 助教 (80767210)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ホスホイノシタイド / PI3キナーゼ / エンドサイトーシス / 循環調節 / 平滑筋収縮 / PI3K / ミトコンドリア / メンブレントラフィッキング / PI3K-C2α / PI3K-C2β / 周生期循環適応 |
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| Outline of Final Research Achievements |
Class II phosphoinositide3-kinases (PI3Ks), PI3K-C2α andPI3K-C2β, are highly homologous and distinct from class I and class III PI3Ks in catalytic products and domain structures. In contrast to class I and class III PI3Ks, physiological roles of class II PI3Ks are not fully understood. We studied the phenotypes of cardiomyocyte or smooth muscle–specific knockout (KO) mice of PI3K-C2α and PI3K-C2β. Cardiomyocyte specific PI3K-C2α and PI3K-C2β double KO(DKO) mice show heart failure due to collapse of the sarcomere structure and abnormally mitochondrial accumulation. In smooth muscle–specific KO mice show that the pup numbers from single PI3K- C2α–KO and single PI3K-C2β–KO mothers were similar to those of control, but those from double KO(DKO)mothers were smaller compared with control.
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| Academic Significance and Societal Importance of the Research Achievements |
PI3Kは3つのクラスが存在し、I型PI3KはPI(3,4,5)P3を産生して細胞遊走や細胞増殖に関与し、III型PI3KはPI(3)Pを産生してオートファジーを制御する。一方II型PI3Kの機能は、申請者のグループがPI3K-C2α KOマウスを報告するまで不明であった。内皮細胞においてPI3K-C2αは主としてPI(3,4)P2を産生し、受容体エンドサイトーシスに必須である。II型PI3Kは、I型・III型PI3Kとは異なる、独自の生命維持機能を担っている。II型PI3K機能の類似の研究はなく、周生期適応におけるII型PI3K機能の解明により、PIによる膜動現象制御の理解が進展する。
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages.2018
Author(s)
Zhao J, Okamoto Y, Asano Y, Ishimaru K, Aki S, Yoshioka K, Takuwa N, Wada T, Inagaki Y, Takahashi C, Nishiuchi T, Takuwa Y.
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Journal Title
PLoS One
Volume: 13
Issue: 5
Pages: e0197604-e0197604
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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