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Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

フォーマット:
論文
責任表示:
Yoshioka, Kazuaki ; Yoshida, Kotaro ; Cui, Hong ; Wakayama, Tomohiko ; Takuwa, Noriko ; Okamoto, Yasuo ; Du, Wa ; Qi, Xun ; Asanuma, Ken ; Sugihara, Kazushi ; Aki, Sho ; Miyazawa, Hidekazu ; Biswas, Kuntal ; Nagakura, Chisa ; Ueno, Masaya ; Iseki, Shoichi ; Schwartz, Robert J. ; Okamoto, Hiroshi ; Sasaki, Takehiko ; Matsui, Osamu ; Asano, Masahide ; Adams, Ralf H. ; Takakura, Nobuyuki ; Takuwa, Yoh
言語:
英語
出版情報:
Nature Publishing Group, 2012-10-01
著者名:
Yoshioka, Kazuaki
Yoshida, Kotaro
Cui, Hong
Wakayama, Tomohiko
Takuwa, Noriko
Okamoto, Yasuo
Du, Wa
Qi, Xun
Asanuma, Ken
Sugihara, Kazushi
Aki, Sho
Miyazawa, Hidekazu
Biswas, Kuntal
Nagakura, Chisa
Ueno, Masaya
Iseki, Shoichi
Schwartz, Robert J.
Okamoto, Hiroshi
Sasaki, Takehiko
Matsui, Osamu
Asano, Masahide
Adams, Ralf H.
Takakura, Nobuyuki
Takuwa, Yoh
続きを見る
掲載情報:
Nature Medicine
ISSN:
1078-8956  CiNii Articles  Webcat Plus  JAIRO
巻:
18
通号:
10
開始ページ:
1560
終了ページ:
1569
バージョン:
author
概要:
The class II α-isoform of phosphatidylinositol 3-kinase (PI3K-C2α) is localized in endosomes, the trans-Golgi network and clathrin-coated vesicles; however, its functional role is not well understood. Global or endothelial-cell- specific deficiency of PI3K-C2α resulted in embryonic lethality caused by defects in sprouting angiogenesis and vascular maturation. PI3K-C2α knockdown in endothelial cells resulted in a decrease in the number of PI3-phosphate-enriched endosomes, impaired endosomal trafficking, defective delivery of VE-cadherin to endothelial cell junctions and defective junction assembly. PI3K-C2α knockdown also impaired endothelial cell signaling, including vascular endothelial growth factor receptor internalization and endosomal RhoA activation. Together, the effects of PI3K-C2α knockdown led to defective endothelial cell migration, proliferation, tube formation and barrier integrity. Endothelial PI3K-C2α deficiency in vivo suppressed postischemic and tumor angiogenesis and diminished vascular barrier function with a greatly augmented susceptibility to anaphylaxis and a higher incidence of dissecting aortic aneurysm formation in response to angiotensin II infusion. Thus, PI3K-C2α has a crucial role in vascular formation and barrier integrity and represents a new therapeutic target for vascular disease.<br />In Press / 2013-03-18公開予定. 続きを見る
URL:
http://hdl.handle.net/2297/32825

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Aki, Sho, Yoshioka, Kazuaki, Okamoto, Yasuo, Takuwa, Noriko, Takuwa, Yoh

American Society for Biochemistry and Molecular Biology

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American Association for Cancer Research

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American Society for Clinical Investigation

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Elsevier (Cell Press)

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Histochemical Society

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