2013 Fiscal Year Final Research Report
Class II PI3 kinase C2alpha has an essential role in angiogenesis and vascular homeostasis through regulating endosomal trafficking
| Project/Area Number |
23590257
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 |
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| Project Period (FY) |
2011 – 2013
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| Keywords | PI3キナーゼ / 血管内皮細胞 / 血管新生 / 細胞内小胞輸送 / 解離性大動脈瘤 / 血管透過性 / 低分子量Gタンパク質 / ノックアウトマウス |
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| Research Abstract |
Although class I PI3Ks and class III Vps34 are well-characterized, the physiological roles of PI3K class IIa (C2a) remain largely unknown. Global C2a-null mice and EC-specific C2a conditional KO mice showed embryonic lethality due to defects in sprouting angiogenesis and vascular maturation. In cultured ECs, siRNA-mediated knockdown of C2a resulted in impaired endosomal trafficking. C2a knockdown also impaired cell signaling including VEGF receptor-2 internalization and RhoA activation on endosomes, but not Akt and ERK. Consequently, endosomal delivery of VE-cadherin to EC junctions was disturbed, leading to defects in VE-cadherin transport and assembly and barrier integrity. C2a haplo-insufficient mice exhibited defective postnatal angiogenesis and vascular barrier integrity with a higher incidence of dissecting aortic aneurysm formation on angiotensin-II infusion. Thus, C2a plays a crucial role in vascular formation and barrier integrity.
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[Journal Article] Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function2012
Author(s)
YoshiokaK , Yoshida K, Cui H, Wakayama T, Takuwa N, Okamoto Y, Du W, Qi X, Asanuma K, Sugihara K, Aki S, Miyazawa H, Biswas K, Nagakura C, Ueno M, Iseki S, Schwartz RJ, Okamoto H, Sasaki T, Matsui O, Asano M, Adams RH, Takakura N, and Takuwa Y
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Journal Title
NatureMed
Volume: 18 (10)
Pages: 1560-1569
DOI
Peer Reviewed
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[Journal Article] Overexpression of sphingosine kinase 1 prevents ceramide accumulation and ameliorates muscle insulin resistance in high fat-fed mice2012
Author(s)
Bruce CR, Risis S, Babb JR, Yang C, Kowalski GM, Selathurai A, Lee-Young RS, Weir JM, Yoshioka K , Takuwa Y, Meikle PJ, Pitson SM and Febbraio MA
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Journal Title
Diabetes
Volume: 61
Pages: 3148-3155
DOI
Peer Reviewed
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[Presentation]2012
Author(s)
Biswas K, Yoshioka K ., Takuwa N, Okamoto Y, Takuwa Y
Organizer
第35回日本分子生物学会
Place of Presentation
福岡
Year and Date
20121211-14
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[Presentation] Endothelial class II PI3K-C2αhas an essential role for physiological and pathological angiogenesis2011
Author(s)
Yoshioka K ., Kotaro Yoshida, Hong Cui, Xun Qi, Tomohiko Wakayama, Noriko Takuwa, Yasuo Okamoto, Kazushi Sugihara, Sho Aki, Kuntal Biswas, Masahide Asano, Yoh Takuwa
Organizer
日本分子生物学会第11回春季シンポジウム
Place of Presentation
石川県立音楽堂(金沢)
Year and Date
20110525-26
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