GMU-GIBH Joint School of Life Sciences, Center of Reproductive Medicine, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510182, China.
Healthcare Department, Agency for Offices Administration, Haidian District, Beijing 100082, China.
Aging (Albany NY). 2020 Nov 16;12(23):23960-23973. doi: 10.18632/aging.104073.
Increased vascular endothelial permeability can disrupt vascular barrier function and further lead to multiple human diseases. Our previous reports indicated that particulate matter 2.5 (PM2.5) can enhance the permeability of vascular endothelial cells. However, the regulatory mechanism was not comprehensively demonstrated. Therefore, this work elucidated this mechanism by demonstrating that PM2.5 can increase the permeability of HUVECs by inhibiting the expression of Hickson compact group 18 (HCG18). Moreover, we demonstrated that lncRNA HCG18 functioned as a ceRNA for miR-21-5p and led to the derepression of its target SOX7, which could further transcriptionally activate the expression of VE-cadherin to regulate the permeability of HUVECs. In this study, we provide evidence that HCG18/miR-21-5p/SOX7/VE-cadherin signaling is involved in PM2.5-induced vascular endothelial barrier dysfunction.
血管内皮通透性增加可破坏血管屏障功能，进而导致多种人类疾病。我们之前的报告表明，细颗粒物 2.5（PM2.5）可增强血管内皮细胞的通透性。然而，其调节机制尚未得到全面证实。因此，本工作通过证明 PM2.5 可以通过抑制 Hickson 紧密群 18（HCG18）的表达来增加 HUVEC 的通透性来阐明这一机制。此外，我们证明 lncRNA HCG18 作为 miR-21-5p 的 ceRNA，导致其靶基因 SOX7 去抑制，进而转录激活 VE-cadherin 的表达，从而调节 HUVEC 的通透性。在这项研究中，我们提供了证据表明 HCG18/miR-21-5p/SOX7/VE-cadherin 信号通路参与了 PM2.5 诱导的血管内皮屏障功能障碍。
