kindlins调节整合素和生长因子依赖的尿道芽形成
Shensen Li1, Fabian Bock1,2,3, Olga Viquez1
1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
概括
kindlins对脏发育至关重要,它调解尿道芽形成和分支的必要生长因子信号. 如果没有kindlins,脏的发育就会完全失败.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 收集系统的发育依赖于尿道 (UB) 的分支.
- 这个过程涉及细胞外矩阵与β1-整合素受体的相互作用.
- 整合素结合亲和力是由kindlins调节的,kindlins与β子单元尾巴相互作用.
研究的目的:
- 研究kindlins在调节发育过程中的β1-整合素功能中的作用.
- 阐明kindlin介导的整合蛋白结合对UB分支和收集管道 (CD) 形成的具体贡献.
主要方法:
- 在UB中产生具有突变β1-整合素缺乏kindlin结合点的小鼠.
- 对这些小鼠的发育和CD细胞功能的分析.
- 产生和分析kindlin-knockout小鼠和CD细胞.
主要成果:
- 患有kindlin结合缺陷β1-整合素的小鼠表现出骨髓缺血和中度分支缺陷.
- 突变的CD细胞表现出受损的管体生成,扩散和粘附,但保留了生长因子信号.
- 在Kindlin淘汰赛中,小鼠出现了,这表明UB芽完全失败.
- Kindlin-knockout CD细胞未能扩散,粘附或对生长因子做出反应,即使有联结的整体素.
结论:
- Kindlins 调节整合素功能和关键生长因子信号通路.
- kindlins对于初始尿管芽的形成和随后的脏发育至关重要.
- 在脏发育中,kindlin-binding整体与kindlin蛋白本身的不同作用.
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