{"created":"2023-07-27T06:31:21.372547+00:00","id":16742,"links":{},"metadata":{"_buckets":{"deposit":"0f0dffda-6158-470d-8a55-283dd874f619"},"_deposit":{"created_by":3,"id":"16742","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"16742"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00016742","sets":["1132:1137:1270:1284"]},"author_link":["30622"],"item_7_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2013-06-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageEnd":"34","bibliographicPageStart":"31","bibliographicVolumeNumber":"122","bibliographic_titles":[{"bibliographic_title":"金沢大学十全医学会雑誌 = Journal of the Juzen Medical Society"}]}]},"item_7_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The class II a-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. © 2012 Nature America, Inc. All rights reserved. ホスファチジルイノシトール3-キナーゼのクラスIIαアイソフォーム（PI3K-C2α）は、エンドソーム、トランスゴルジネットワークおよびクラスリン被覆小胞に局在するが、その機能的役割は十分に解明されていない。PI3K-C2αを全身あるいは内皮細胞特異的に欠損させると、血管新生過程の出芽の異常や血管成熟異常により、胎生致死となった。内皮細胞でPI3K-C2αをノックダウンすると、PI3-リン酸に富むエンドソーム数の減少、エンドソーム輸送の障害、内皮細胞接着装置へのVE-カドヘリンの送達異常および細胞接着装置の組み立て異常が起こった。PI3K-C2αのノックダウンはまた、血管内皮増殖因子受容体の内在化やエンドソームのRhoA活性化などの内皮細胞シグナル伝達の異常も引き起こした。まとめると、PI3K-C2αノックダウンの影響は、内皮細胞の遊走、増殖、管腔形成および血管障壁健全性の異常を生じる。 in vivo で内皮のPI3K-C2αを欠損させると、虚血後および腫瘍での血管新生が抑制され、また血管障壁機能が減弱するとともに、アナフィラキシーに対する感受性の大幅な増強とアンギオテンシンII注入に応答した解離性大動脈瘤形成の発生率上昇が引き起こされた。したがって、PI3K-C2αは、血管形成と血管障壁の健全性に非常に重要な役割を担っており、血管系疾患の新しい治療標的となる。","subitem_description_type":"Abstract"}]},"item_7_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"[総説 / Reviews][博士課程優秀論文] 第11回 高安賞最優秀論文賞受賞論文, Nature Medicine 18 (10) , pp. 1560-1569(2012年10月掲載), Kazuaki Yoshioka,Kotaro Yoshida,Hong Cui,Tomohiko Wakayama,Noriko Takuwa,Yasuo Okamoto,Wa Du, Xun Qi,Ken Asanuma,Kazushi Sugihara,Sho Aki, Hidekazu Miyazawa,Kuntal Biswas,Chisa Nagakura,Masaya Ueno,Shoichi Iseki,Robert J Schwartz,Hiroshi Okamoto,Takehiko Sasaki,Osamu Matsui,Masahide Asano,Ralf H Adams,Nobuyuki Takakura & Yoh Takuwa \"Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function\" http://dx.doi.org/10.1038/nm.2928, 最終稿の全文をKURAで公開中(関連URL参考)","subitem_description_type":"Other"}]},"item_7_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"金沢大学十全医学会 = The Juzen Medical Society Kanazawa University"}]},"item_7_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://dspace.lib.kanazawa-u.ac.jp/dspace/handle/2297/32825","subitem_relation_type_select":"URI"}}]},"item_7_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AN00044397","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0022-7226","subitem_source_identifier_type":"ISSN"}]},"item_7_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"吉田, 耕太郎"}],"nameIdentifiers":[{"nameIdentifier":"30622","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"30645130","nameIdentifierScheme":"金沢大学研究者情報","nameIdentifierURI":"http://ridb.kanazawa-u.ac.jp/public/detail.php?kaken=30645130"},{"nameIdentifier":"30645130","nameIdentifierScheme":"研究者番号","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000030645130"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-04"}],"displaytype":"detail","filename":"AN00044397-122-2-31-34.pdf","filesize":[{"value":"830.4 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"AN00044397-122-2-31-34.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/16742/files/AN00044397-122-2-31-34.pdf"},"version_id":"fd102c55-e01f-4ac3-ac95-5d903ecd5a7a"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"クラスIIα 型phosphatidylinositel 3キナーゼは, 血管内皮細胞において小胞輸送の制御を介して血管新生及び血管バリア機能に必要である","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"クラスIIα 型phosphatidylinositel 3キナーゼは, 血管内皮細胞において小胞輸送の制御を介して血管新生及び血管バリア機能に必要である"},{"subitem_title":"Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function","subitem_title_language":"en"}]},"item_type_id":"7","owner":"3","path":["1284"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-04"},"publish_date":"2017-10-04","publish_status":"0","recid":"16742","relation_version_is_last":true,"title":["クラスIIα 型phosphatidylinositel 3キナーゼは, 血管内皮細胞において小胞輸送の制御を介して血管新生及び血管バリア機能に必要である"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-28T00:15:00.775219+00:00"}