2010 Fiscal Year Final Research Report
Mechanistic analysis of blood vessel formation in class II PI3 kinase C2・ knockout mouse
| Project/Area Number |
20590207
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOSHIOKA Kazuaki Kanazawa University, 医学系, 助教 (80333368)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 血管新生 / 血管障害 / PI3キナーゼ / 血管透過性 / 解離性大動脈瘤 / ノックアウトマウス / モデル動物 |
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| Research Abstract |
Phosphatidylinositol-3-OH kinase (PI3K) family, which comprises three classes, regulates a diverse array of cellular processes through the generation of 3-phosphoinositides. Although class I PI3Ks including p110α, p110β, p110δ and p110γ isoforms were well characterized among three classes, the in vivo physiological functions of class II PI3Ks, which comprise three members PI3K-C2α (C2α), C2β and C2γ, remain largely unknown. We found that Pik3c2a gene-global disruption (C2α KO) and conditional loss of C2α in endothelial cells (ECs) in mice, but not in vascular smooth muscles (VSMCs) and cardiomyocytes, caused embryonic lethality due to impairment of developmental angiogenesis characterized by incomplete EC sprouting and mural-cell (VSMCs and pericytes) coverage. Finally, C2α-haploinsufficient mice are alive, but exhibit vascular hyperpermeability and a higher incidence of dissecting aortic aneurysms with rupture on angiotensin-II (AngII) infusion. These results provide the first evidence that C2α plays a novel essential role in endothelial physiology, particularly angiogenesis and barrier integrity, through regulating endosomal trafficking and underscore broader roles for PI3K family members in vascular physiology.
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[Journal Article] S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species.2010
Author(s)
Takuwa N, Ohkura S, Takashima S, Ohtani K, Okamoto Y, Tanaka T, Hirano K, Usui S, Wang F, Du W, Yoshioka K, et al.
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Journal Title
Cardiovasc.Res. 85
Pages: 484-493
Peer Reviewed
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[Presentation] Bimodal actions of the cardiac sphingosine-1-phosphate signaling revealed in sphingosine kinase 1transgenic mice : S1P3-mediated, Rho- and active oxygen-dependent, chronic progression ofspontaneous cardiac remodeling and cardioprotection against acutely imposed ischemia reperfusion injury in sphingosine kinase 1 transgenic mice.2010
Author(s)
Takuwa N, Ohkura S, Takashima S, Ohtani K, Usui S, Okamoto Y, Wang F, Du W, Yoshioka K, Takuwa Y
Organizer
第87回日本生理学会大会
Place of Presentation
岩手
Year and Date
20100519-20100521
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[Presentation] Development of cardiac fibrosis in sphingosine kinase 1 transgenic mice through an S1P3 receptor-mediated, reactivec oxygen species-dependent process2010
Author(s)
Takuwa N, Ohkura S, Takashima S, Ohtani K, Okamoto Y, Usui S, Yoshioka K, Takamura M, Kaneko S, Takuwa Y
Organizer
第74回日本循環器学会
Place of Presentation
京都国際会議場(京都)
Year and Date
20100305-20100307
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