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Role of Src in angiopoietin 1-induced capillary morphogenesis of endothelial cells: Effect of chronic hypoxia on Src inhibition by PP2.
http://hdl.handle.net/10069/22292
http://hdl.handle.net/10069/22292f3efef61-c587-469d-bf16-7717cc04ae23
名前 / ファイル | ライセンス | アクション |
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CelSig19_472.pdf (1.6 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2009-10-27 | |||||
タイトル | ||||||
タイトル | Role of Src in angiopoietin 1-induced capillary morphogenesis of endothelial cells: Effect of chronic hypoxia on Src inhibition by PP2. | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Angiopoietin 1 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Capillary morphogenesis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Src | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PP2 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Chronic hypoxia | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Kanda, Shigeru
× Kanda, Shigeru× Kanetake, Hiroshi× Miyata, Yasuyoshi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Signal transduction pathways leading to angiopoietin 1 (Ang1)-induced capillary morphogenesis by endothelial cells remain poorly defined. Angiogenic cellular responses by endothelial cells may be modulated in vivo by chronic hypoxia, such as that induced by tumors. Here, we studied Ang1-induced capillary morphogenesis in human umbilical-vein endothelial cells (HUVECs) cultured chronically under normoxic (21% oxygen) or hypoxic (1.5% oxygen) conditions. Downregulation of Src using a small interfering RNA (siRNA) inhibited Ang1-induced capillary morphogenesis of HUVECs cultured under both conditions by blocking cell spreading and protrusion. Ang1 upregulated the Src-dependent secretion of vascular endothelial growth factor-A (VEGF-A). Blockade of endogenous VEGF-A also inhibited Ang1-induced capillary morphogenesis. Addition of exogenous VEGF-A restored cell spreading and protrusion, leading to Ang1-induced capillary morphogenesis of Src siRNA-treated HUVECs, suggesting that Ang1-induced VEGF-A secretion through Src was required for capillary morphogenesis. PP2 inhibited both Ang1-induced capillary morphogenesis and Src activation in HUVECs cultured under normoxic conditions, but the PP2 activity was significantly impaired in HUVECs cultured under hypoxic conditions. Expression of multidrug resistance-associated protein 1 (MRP 1) was upregulated in hypoxic HUVECs, and treatment with MRP 1 siRNA restored the inhibitory action of PP2. Taken together, our results suggest that Ang1 induces capillary morphogenesis in HUVECs through Src-dependent upregulation of endogenous VEGF-A. Conditions of chronic hypoxia impaired the effect of PP2, possibly via MRP 1. | |||||
書誌情報 |
Cellular signalling 巻 19, 号 3, p. 472-480, 発行日 2007-03 |
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出版者 | ||||||
出版者 | Elsevier Inc. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 08986568 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10671314 | |||||
PubMed番号 | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | PMID | |||||
関連識別子 | 16949254 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.cellsig.2006.07.014 | |||||
権利 | ||||||
権利情報 | Copyright c 2006 Elsevier Inc. All rights reserved. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Cellular signalling, 19(3), pp.472-480; 2007 |