YAP1识别炎症和机械线索,通过促进细胞存活和纤维化来加剧良性前列腺增生
Dongxu Lin1, Changcheng Luo1, Pengyu Wei1
1Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 5, 2023
概括
炎症诱导的机械变化激活YAP1通路,促进良性前列腺增生症 (BPH) 中的细胞存活和纤维化. 针对这个轴可能会提供新的BPH治疗方法.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 细胞生物学 细胞生物学
- 生物医学工程 生物医学工程
背景情况:
- 慢性前列腺炎症有助于良性前列腺激增症 (BPH) 的发展.
- 是的相关蛋白1 (YAP1) 的作用是关键的调节器官大小和机械信号,在炎症驱动的BPH是不清楚的.
研究的目的:
- 调查YAP1在炎症诱导的BPH中的参与.
- 分析YAP1表达与BPH纤维化之间的相关性.
- 阐明YAP1激活影响前列腺细胞存活和纤维化的机制.
主要方法:
- 在人类和老鼠BPH标本中分析YAP1表达和下游基因.
- 对YAP1表达,纤维化严重程度和临床参数之间的相关性分析.
- 在体外研究涉及BPH-1和WPMY-1细胞中的YAP1沉默.
- 研究RhoA/ROCK1通路和细胞骨重塑.
主要成果:
- 在与炎症相关的BPH中,YAP1及其下游基因表达显著上调.
- YAP1表达与纤维化严重程度和临床结果正相关.
- 通过抑制EMT和ECM沉积,YAP1沉默减少了细胞增殖,增加了细胞亡,并逆转了纤维化.
- 炎症刺激和矩阵刚性协同激活了RhoA/ROCK1通路,导致YAP1的激活.
结论:
- 炎症引起的机械硬度激活了BPH中的RhoA/ROCK1/F-actin/YAP1轴.
- 这种激活促进前列腺细胞存活和纤维化,加速BPH的进展.
- 准YAP1通路为BPH提供了潜在的治疗策略.
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