GPR68感官流动,对于血管生理学至关重要
Jie Xu1, Jayanti Mathur1, Emilie Vessières2
1Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
Cell
|April 21, 2018
概括
研究人员确定G蛋白结合受体68 (GPR68) 是内皮细胞中血液流动的关键传感器. 这一发现对于理解诸如高血压和动脉样硬化等血管疾病至关重要.
科学领域:
- 血管生物学 血管生物学
- 机械生物学 机械生物学
- 心血管生理学心血管生理学
背景情况:
- 机械传导在血管生物学中至关重要,通过流媒扩张 (FMD) 调节血管阻力.
- 内皮功能障碍,标志着受损的口病,先于血管疾病,如高血压和动脉样硬化.
- 在内皮细胞中感知剪切应力的特定分子在很大程度上未被确定.
研究的目的:
- 确定分子机制和特定分子负责感知内皮细胞中剪切应力.
- 调查已识别的分子在流媒体扩张和血管重塑中的作用.
主要方法:
- 为培养细胞开发了一种384井切割应激选系统.
- 利用机械敏感细胞系检测剪切应力激活的过渡物.
- 选了一个聚焦的RNAi库来识别切割应激反应关键基因.
- 在小鼠中腔动脉小管中检查了GPR68的表达.
- 在Gpr68缺乏的小鼠中评估了口病和血管改造.
主要成果:
- 确定了G蛋白结合受体68 (GPR68) 作为内皮细胞剪切应激反应所需和足够的.
- GPR68在直径小的阻力动脉的内皮细胞中表达.
- 缺乏Gpr68的小鼠表现出严重受损的急性口炎和慢性流媒体外向重塑.
- GPR68在动脉内皮中起到重要的流量传感器的作用.
结论:
- GPR68 是一种关键的分子组件,用于感知动脉内皮中的剪切应力.
- GPR68在心血管病理生理学中起着重要作用,特别是在调节血管抵抗和重塑方面.
- 针对GPR68可能为与内皮功能障碍相关的血管疾病提供新的治疗策略.
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