Molecular mechanisms of postnatal angiogenesis and neurogenesis

出生后血管生成和神经发生的分子机制

• 批准号: 23249020
• 负责人: TAKAHASHI Masahide
• 金额: $ 31.12万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23249020/
• 关键词: Girdin; Akt; 細胞運動; 神経新生; 血管新生; チロシンリン酸化; focal adhesion; 遺伝子改変マウス; Daple; Disheveled; Rac; Wntシグナル

To identify the cellular population responsible for the phenotype of girdin KO mice, newly generated girdin flox mice were crossed with nestin-promoter driven Cre-transgenic mice to obtain girdin conditional knockout mice.Our findings suggested that girdin expression in nestin cell lineage is responsible for the phenotype of girdin KO mice.We used a mouse model of pathological ocular neovascularization: oxygen-induced retinopathy.Pathological neovascularization was decreased in S1416A knockin mice. The results demonstrate that girdin and its phosphorylation play an important role in neonatal vascular development and in pathological neovascularization in the retina.We also found that depletion of girdin attenuated venous smooth muscle cells migration and proliferation in vitro and intimal hyperplasia in vein grafts in vivo.Moreover, we demonstrated that a girdin family protein, Dishevelled-associating protein Daple, controls the non-canonical Wnt/Rac pathway and cell motility

为了鉴定导致 girdin KO 小鼠表型的细胞群，将新生成的 girdin flox 小鼠与巢蛋白启动子驱动的 Cre 转基因小鼠杂交，以获得 girdin 条件敲除小鼠。我们的研究结果表明，巢蛋白细胞谱系中的 girdin 表达负责girdin KO 小鼠的表型。我们使用了病理性眼部新生血管形成的小鼠模型：氧诱导的视网膜病变。病理性新生血管形成在S1416A 敲入小鼠。结果表明，girdin 及其磷酸化在新生儿血管发育和视网膜病理性新生血管形成中发挥重要作用。我们还发现，girdin 的消耗减弱了体外静脉平滑肌细胞的迁移和增殖以及体内静脉移植物的内膜增生。此外，我们证明了 girdin 家族蛋白，Dishevelled 关联蛋白 Daple，控制非经典 Wnt/Rac 通路和细胞运动

项目成果

Aktの基質蛋白Girdinのがんの進展、血管新生における役割

Akt 底物蛋白 Girdin 在癌症进展和血管生成中的作用

• 发表时间: 2012
• 作者: Nakayama T;Kurobe H;Sugasawa N;Kinoshita H;Higashida M;Matsuoka Y;Yoshida Y;Hirata Y;Sakata M;Maxfield M;Shimabukuro M;Takahama Y;Sata M;Tamaki T;Kitagawa T;Tomita S.;Kazuhisa Sekimizu;Nakanishi K.;児谷吉紘，西村伸一，珠玖隆行;高橋雅英
• 通讯作者: 高橋雅英

The Actin-Binding Protein Girdin and Its Akt-Mediated Phosphorylation Regulate Neointima Formation After Vascular Injury

• DOI: 10.1161/circresaha.110.236174
• 发表时间: 2011-05-13
• 期刊: CIRCULATION RESEARCH
• 影响因子: 20.1
• 作者: Miyake, Hiroshi;Maeda, Kengo;Murohara, Toyoaki
• 通讯作者: Murohara, Toyoaki

Girdin is an intrinsic regulator of neuroblast chain migation in the Rostral migratory stream of the postnatal brain

Girdin 是出生后大脑头端迁移流中神经母细胞链迁移的内在调节因子

• 发表时间: 2011
• 期刊: Journal of Neuroscience
• 影响因子: 5.3
• 作者: Okazaki;K.;Y. Kuroda;K. Taguchi;H. Takahashi;N. Koga and S. Ikeda;Yun Wang
• 通讯作者: Yun Wang

Roles of the Akt substrate Girdin in cancer progression and angiogenesis.

Akt 底物 Girdin 在癌症进展和血管生成中的作用。

• 发表时间: 2014
• 作者: Yoo J-S;Kato H;Nagamine Y;Fujita T.;上谷ひとみ;村田満;Masahide Takahashi
• 通讯作者: Masahide Takahashi

Role of the Akt substrate Girdin in cancer progression and angiogenesis

Akt 底物 Girdin 在癌症进展和血管生成中的作用

• 发表时间: 2012
• 作者: 安川淳一朗;松本靖彦;林陽平;宮﨑真也;関水和久;Masahide Takahashi
• 通讯作者: Masahide Takahashi