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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:
- 掲載情報:
- Nature Medicine
- ISSN:
- 1078-8956
- 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
類似資料:
American Society for Biochemistry and Molecular Biology | |
American Association for Cancer Research | |
Physiological Society of Japan 日本生理学会 / Springer Nature | |
Endocrine Society / Oxford University Press |
金沢大学がん研究所 = Kanazawa University Cancer Research Institute |
American Society for Clinical Investigation | |
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