PDF(Pubmed)
Abstract：
Exposure to microgravity during spaceflight induces the alterations in endothelial cell function associated with post-flight cardiovascular deconditioning. PIEZO1 is a major mechanosensitive ion channel that regulates endothelial cell function. In this study, we used a two-dimensional clinostat to investigate the expression of PIEZO1 and its regulatory mechanism on human umbilical vein endothelial cells (HUVECs) under simulated microgravity. Utilizing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, we observed that PIEZO1 expression was significantly increased in response to simulated microgravity. Moreover, we found microgravity promoted endothelial cells migration by increasing expression of PIEZO1. Proteomics analysis highlighted the importance of C-X-C chemokine receptor type 4(CXCR4) as a main target molecule of PIEZO1 in HUVECs. CXCR4 protein level was increased with simulated microgravity and decreased with PIEZO1 knock down. The mechanistic study showed that PIEZO1 enhances CXCR4 expression via Ca2+ influx. In addition, CXCR4 could promote endothelial cell migration under simulated microgravity. Taken together, these results suggest that the upregulation of PIEZO1 in response to simulated microgravity regulates endothelial cell migration due to enhancing CXCR4 expression via Ca2+ influx.
摘要：
在太空飞行中暴露于微重力会引起与飞行后心血管疾病相关的内皮细胞功能改变。PIEZO1是调控内皮细胞功效的主要机械敏感离子通道。在这项研究中,我们使用二维clinostat研究了模拟微重力下PIEZO1在人脐静脉内皮细胞（HUVECs）上的表达及其调节机制。利用定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹分析，我们观察到PIEZO1表达在模拟微重力下显著增加。此外，我们发现微重力通过增加PIEZO1的表达促进内皮细胞迁移.蛋白质组学分析强调了C-X-C趋化因子受体4型（CXCR4）作为HUVEC中PIEZO1的主要靶分子的重要性。CXCR4蛋白水平随着模拟微重力而升高，随着PIEZO1敲低而降低。机制研究表明，PIEZO1通过Ca2流入增强CXCR4的表达。此外,CXCR4在模拟微重力条件下可促进内皮细胞迁移。一起来看,这些结果表明，响应模拟微重力的PIEZO1上调调节内皮细胞迁移，这是由于通过Ca2+内流增强CXCR4的表达。
