Identification of Hic-5 as a novel regulatory factor for integrin aIIbb3 activation and platelet aggregation in mice.

鉴定 Hic-5 作为小鼠体内整合素 aIIbb3 激活和血小板聚集的新型调节因子。

• 批准号: 23791090
• 负责人: KANEYAMA Shuri
• 金额: $ 2.58万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791090/
• 关键词: 血栓・止血学; 血小板; 細胞接着斑分子; Hic-5; インテグリン

Hic-5, a member of the paxillin family, serves as a focal adhesion adaptor protein associated with aIIbb3. Hic-5 function in aIIbb3 activation and subsequent platelet aggregation remains unknown. To address this question, platelets from Hic-5-/- mice were analyzed. Hic-5-/- mice displayed a significant hemostatic defect and resistance to thromboembolism, which were explained in part by weaker thrombin-induced aggregation in Hic-5-/- platelets. Mechanistically, Hic-5-/- platelets showed limited activation of aIIbb3 upon thrombin treatment. Morphological alteration in Hic-5-/- platelets after thrombin stimulation on fibrinogen plates was also limited. As a direct consequence, the quantity of actin co-immunoprecipitating with the activated aIIbb3 was smaller in Hic-5-/- platelets than in wild-type platelets.We identified Hic-5 as a novel and specific regulatory factor for thrombin-induced aIIbb3 activation and subsequent platelet aggregation in mice.

Hic-5是paxillin家族的一员，是与aIIbb3相关的局灶黏附接头蛋白。Hic-5在aIIbb3激活和随后的血小板聚集中的功能尚不清楚。为了解决这个问题，我们分析了Hic-5-/-小鼠的血小板。Hic-5-/-小鼠表现出明显的止血缺陷和对血栓栓塞的抵抗，部分原因是Hic-5-/-血小板中凝血酶诱导的聚集较弱。在机制上，Hic-5-/-血小板在凝血酶治疗后表现出有限的aIIbb3活化。纤维蛋白原板上凝血酶刺激后Hic-5-/-血小板的形态学改变也有限。直接结果是，Hic-5-/-血小板中肌动蛋白与活化的aIIbb3共免疫沉淀的数量比野生型血小板少。我们发现Hic-5是一种新的特异性调节因子，可调节凝血素诱导的aIIbb3激活和随后的小鼠血小板聚集。

项目成果

Hic-5 deficiency blocks the development of angiotensin II-induced abdominal aortic aneurysms by inhibiting c-Jun N-terminal kinase 2 in mice.

Hic-5 缺陷通过抑制小鼠体内的 c-Jun N 末端激酶 2 来阻止血管紧张素 II 诱导的腹主动脉瘤的发展。

• 发表时间: 2013
• 作者: 金山朱里;雷小峰;有田茂子;宮崎拓郎;宮崎章
• 通讯作者: 宮崎章

Native incretins supress the proliferation and migration of vascular smooth muscle cells

天然肠促胰岛素抑制血管平滑肌细胞的增殖和迁移

• 发表时间: 2011
• 作者: Tomoyasu M;Kim-Kaneyama JR et al.
• 通讯作者: Kim-Kaneyama JR et al.

Kim-Kaneyama JR, Miyazaki A et al.

Kim-Kaneyama JR、宫崎 A 等人。

• 发表时间: 2011
• 作者: 齊藤由紀子,竹田正秀,伊藤亘,木原純子,植木重治,小林良樹,守時由起,糸賀正道,今野泰典,茆原真実,萱場広之,茆原順一;Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling
• 通讯作者: Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling

Hic-5 deficiency blocks the development of angiotensin II-induced abdominal aortic aneurysms in mice

Hic-5 缺陷可阻止血管紧张素 II 诱导的小鼠腹主动脉瘤的发展

• 发表时间: 2012
• 作者: Lei XF;Kim-Kaneyama JR;Arita S;Miyazaki T;Miyazaki A
• 通讯作者: Miyazaki A

Deletion of hydrogen peroxide-inducible clone-5 inhibits atherosclerotic plaque formation in Apolipoprotein E knockout mice

过氧化氢诱导克隆 5 的缺失抑制载脂蛋白 E 敲除小鼠中动脉粥样硬化斑块的形成

• 发表时间: 2013
• 作者: ShigekoArita;Joo-ri Kim-Kaneyama;Xiao-Feng Lei;Takuro Miyazaki;Akira Miyazaki
• 通讯作者: Akira Miyazaki