拥挤会诱导活细胞挤出,以维持表皮细胞中的同居细胞数量
George T Eisenhoffer1, Patrick D Loftus, Masaaki Yoshigi
1Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive, Salt Lake City, Utah 84112, USA.
Nature
|April 17, 2012
概括
细胞增殖引起的上皮质过度拥挤会导致活细胞被挤出,维持屏障功能. 这种由特定的信号通路调节的活细胞挤出,可以防止多余的细胞积累,并可能充当瘤抑制机制.
科学领域:
- 细胞生物学 细胞生物学
- 皮质生物学 皮质生物学
- 恒常状态 (Homeostasis) 是一种恒常状态.
背景情况:
- 表皮组织通过平衡细胞分裂和死亡来维持屏障完整性.
- 虽然死亡的细胞可以触发补偿增殖,但细胞死亡缓解增殖过度拥挤的机制不太清楚.
- 细胞缩细胞挤出是一种已知的机制,可以去除垂死的细胞并保持上皮屏障.
研究的目的:
- 研究表皮细胞管理因增殖和迁移而导致的过度拥挤的机制.
- 为了确定活细胞挤出是否发生在正常上皮质恒常状态.
- 为了识别因拥挤而导致活细胞挤出所涉及的信号通路.
主要方法:
- 实验在体外和体内使用人类,狗和斑马鱼上皮细胞进行.
- 在细胞单层中实验性诱导过度拥挤.
- 分析了神素1-酸盐信号传递,Rho-酶依赖的肌素收缩,以及拉伸激活通道 (包括Piezo1).
- 斑马鱼模型被用来研究破坏拉伸激活通道的体内效应.
主要成果:
- 由增殖和迁移驱动的上皮质过度拥挤,诱导活细胞的挤出,以保持平稳的细胞数量.
- 活细胞挤出是通过actomyosin收缩机械驱动的,涉及到sphingosine 1-phosphate信号和Rho-kinase.
- 挤出是由拉伸激活通道介导的,Piezo1起着至关重要的作用;其破坏导致上皮细胞质量形成.
- 活细胞被挤出在最拥挤的地方,这表明对机械应激的反应.
结论:
- 由于增殖和迁移而导致的上皮质过度拥挤会触发活细胞挤出作为一种恒温机制.
- 这一过程与形挤出不同,它依赖于机械线索和特定的信号通路,包括像Piezo1.1.这样的拉伸激活通道.
- 活细胞挤出可以防止多余细胞的积累,并可以通过消除潜在的超增殖细胞来作为瘤抑制机制.
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