Biochemical process of membrane-associated protein is induced by inflammatory cytokines in cultured lymphatic endothelial cells

培养的淋巴内皮细胞中炎症细胞因子诱导膜相关蛋白的生化过程

• 批准号: 23390283
• 负责人: HIRAKAWA Satoshi
• 金额: $ 12.48万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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/grant/KAKENHI-PROJECT-23390283/
• 关键词: 増殖因子; リンパ管新生; 細胞内シグナル伝達; 遺伝子改変マウス; シグナル伝達; 細胞間接着; ヒアルロン酸; 血管新生; 細胞遊走; 治療; 血管内皮増殖因子; シェディング; 細胞内シグナル

The present study demonstrated that inflammatory cytokines induces the ectodomain shedding of type I transmembrane proteins in cultured human lymphatic endothelial cells. ADAM17 is responsible for the shedding via the activation of MAP kinase pathway in response to vascular endothelial factor (VEGF)-A. Furthermore, the entodomain shedding of membrane-associated protein enhanced the migration of cultured lymphatic endothelial cells in response to VEGF-A. Moreover, double immunofluorescence analysis revealed that the targeted overexpression of VEGF-A promoted the ectodomain shedding of the membrane associated protein cutaneous lymphatic vessels. Therefore, these results indicate, for the first time, that lymphangiogensis is mediated by the biochemical process of membrane-binding proteins in lymphatic endothelial cells in vitro and in vivo.

本研究表明，炎性细胞因子诱导培养的人淋巴内皮细胞中 I 型跨膜蛋白的胞外域脱落。 ADAM17 负责通过响应血管内皮因子 (VEGF)-A 激活 MAP 激酶途径来导致脱落。此外，膜相关蛋白的胞内结构域脱落增强了培养的淋巴内皮细胞响应 VEGF-A 的迁移。此外，双重免疫荧光分析表明，VEGF-A 的靶向过度表达促进了膜相关蛋白皮肤淋巴管的胞外域脱落。因此，这些结果首次表明，淋巴管生成是由体外和体内淋巴内皮细胞膜结合蛋白的生化过程介导的。

项目成果

Multiple milia and comedones as a skin manifestation of systemic amyloidosis

多发性粟丘疹和粉刺是系统性淀粉样变性的皮肤表现

• 发表时间: 2011
• 影响因子: 2.5
• 作者: Funai N; Machida S; Ito T; Hirakawa S; Tokura Y
• 通讯作者: Tokura Y

An approach to fabricate the polymer hollow microneedle that targets dermal lymphatic vessels in the skin.

一种制造针对皮肤真皮淋巴管的聚合物空心微针的方法。

• 发表时间: 2012
• 作者: Satoshi Hirakawa

母斑, 血管腫・脈管形成異常, 山口徹, 今日の治療指針

胎记，血管瘤/血管发育不良，Toru Yamaguchi，今日治疗指南

• 发表时间: 2013
• 作者: 平川聡史

皮膚と循環：血管・リンパ管から考える病態生理

皮肤与循环：从血管和淋巴管考虑的病理生理学

• 发表时间: 2013
• 作者: 平川聡史

A functional role of L YVE-1 in VEGF-A-induced lymphangiogenesis and psoriasis

LYVE-1 在 VEGF-A 诱导的淋巴管生成和银屑病中的功能作用

• 发表时间: 2012
• 作者: Hirakawa S