通过压力力量调节p65核定位和染色质状态
Rajshikhar Gupta1,2, Paulina Schärer1, Yawen Liao1,2
1Laboratory of Multiscale Bioimaging, Paul Scherrer Institut, Villigen, Aargau, Switzerland 5232.
Molecular biology of the cell
|February 5, 2025
概括
瘤微环境 (TME) 研究表明,机械力和化学信号,如瘤缩因子-α (TNFα),相互作用影响支流体纤维细胞. 这种相互作用会影响瘤的进展,并提供新的治疗点.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 瘤微环境 (TME) 对瘤生长和转移至关重要.
- 流体纤维细胞在TME进化和瘤进展中发挥着关键作用.
- 目前针对树突纤维细胞的治疗方法受限于对TME信号传递的理解不足.
研究的目的:
- 为了研究在TME内部的 stromal 纤维细胞中化学和机械信号之间的交叉对话.
- 开发一种模仿TME条件的新型共同培养模型,用于研究树皮细胞反应.
主要方法:
- 用YFP-TNFα释放球体嵌入纤维细胞的原体凝设计了一种培试验.
- 该模型的目标是复制瘤信号和机械应激对树皮反应的反应.
- 在不同条件下分析了p65的核转位和纤维细胞骨变化.
主要成果:
- 瘤亡因子-α (TNFα) 诱导了 p65 在 stromal 纤维细胞中的核转位.
- 压力压力加剧了p65核转移.
- 结合的机械和化学信号导致细胞骨的破坏,并改变了纤维细胞中的染色质状态.
结论:
- 在TME中,细胞因子信号传递和影响肌体细胞的机械力量之间存在显著的交叉对话.
- 开发的球形模型有效地模拟了TME条件,用于研究树皮细胞行为.
- 了解这种交叉谈话对于开发有效的治疗干预措施,以 stromal 纤维细胞为目标至关重要.
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