电脑膜硬度通过RasGRF1-依赖的信号传递来调节肺纤维细胞的生存
Elizabeth Monaghan-Benson1, Julien Aureille2, Christophe Guilluy1
1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
The Journal of biological chemistry
|January 10, 2025
概括
矩阵刚度通过RasGRF1激活提高了肺纤维细胞的存活率. 这一途径涉及AKT和ERK信号,影响FOXO3a和Bim调节细胞存活.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 机械生物学 机械生物学
背景情况:
- 细胞行为受到机械信号的影响,包括细胞外矩阵 (ECM) 刚性.
- 肺纤维细胞的生存是由它们周围的机械环境调节的.
研究的目的:
- 研究ECM度影响肺纤维细胞存活的分子机制.
- 为了确定关键的信号通路和参与机械传导的蛋白质.
主要方法:
- 利用在不同硬度的基板上培养的肺纤维细胞.
- 采用生物化学测试来测量Ras活动和西方模糊用于信号通路分析.
- 使用RNA干扰 (RNAi) 和药理抑制剂来探测特定的信号组件 (RasGRF1,AKT,ERK,FOXO3a,Bim).
主要成果:
- 肺纤维细胞在硬基质上的生存率提高与Ras活性增加相关,由RasGRF1.1介导.
- 增加的Ras活动激活了AKT和ERK信号通路.
- 抑制AKT或ERK信号传递降低了硬基板上的存活率.
- 在软基质上,FOXO3a活性对细胞死亡至关重要,而在硬基质上,其下调导致Bim降解.
- 减少Bim可以提高纤维细胞在软基质上的存活率.
结论:
- 电脑膜硬度激活了肺纤维细胞中的RasGRF1/Ras信号级联.
- 这种级联调节AKT和ERK通路,影响FOXO3a的活性和Bim的表达.
- RasGRF1-AKT-ERK-FOXO3a-Bim轴是细胞存活的关键决定因素,对基质刚度的反应.
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