通过β1整合素的机制感应诱导肝脏生长和存活的血管新生信号
Linda Lorenz1,2,3, Jennifer Axnick1, Tobias Buschmann1,4
1Institute of Metabolic Physiology, Heinrich-Heine University, Düsseldorf, Germany.
Nature
|September 28, 2018
概括
肝脏血管中的血液流动和机械力量激活了血管神经信号. 这些由β1整合素和VEGFR3介导的信号对肝脏生长,肝细胞存活和器官维护至关重要.
科学领域:
- 血管生物学
- 肝病学
- 细胞信号传输
背景情况:
- 血管内皮细胞发出的血管内皮信号对于器官发育,再生和疾病至关重要.
- 这些信号在包括肝脏在内的各种器官中被观察到.
研究的目的:
- 通过使用发育中的肝脏作为模型,研究血管神经信号在肝脏生长中的作用.
- 阐明血液 perfusion 和机械传导调节血管神经信号的机制.
主要方法:
- 肝脏生长速度与血液 perfusion 的相关性.
- 操纵肝脏血流以观察内皮细胞信号的作用.
- 研究β1整合素和血管内皮生长因子受体3 (VEGFR3) 的作用.
- 使用活体肝脏输液和体内肝脏内皮细胞的机械拉伸.
主要成果:
- 肝脏生长速度与血液 perfusion 相对应.
- 血管输液激活β1整合素和VEGFR3.
- 对于肝细胞生长因子的产生,肝细胞存活和肝脏生长,β1整合素和VEGFR3是必不可少的.
- 内皮细胞的机械拉伸足以诱导血管神经信号,促进肝细胞的增殖和存活.
结论:
- 血液 perfusion 和机械传导是肝脏血管蛋白信号的关键调节者.
- 血管内皮细胞将机械线索转化为器官生长和维护的信号.
- 针对这种途径可以为肝脏再生和疾病治疗提供新的策略.
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