PDF(Pubmed)
Abstract：
Acute respiratory infections (ARIs) are associated with high mortality and morbidity. Acute lung injury (ALI) is caused by the activation of immune cells during ARIs caused by viruses such as SARS-CoV-2. Aquaporin 1 (AQP1) is distributed in a variety of immune cells and is related to the occurrence of ALI, but the mechanism is not clear. A reference map of human single cells was used to identify macrophages in COVID-19 patients at the single-cell level. \"FindMarkers\" was used to analyze differentially expressed genes (DEGs), and \"clusterProfiler\" was used to analyze the functions of the DEGs. An M1 macrophage polarization model was established with lipopolysaccharide (LPS) in vitro, and the relationships among AQP1, pyroptosis and M1 polarization were examined by using an AQP1 inhibitor. Transcriptome sequencing and RT-qPCR were used to examine the molecular mechanism by which AQP1 regulates macrophage polarization and pyroptosis. Antigen presentation, M1 polarization, migration and phagocytosis are abnormal in SARS-CoV-2-infected macrophages, which is related to the high expression of AQP1. An M1 polarization model of macrophages was constructed in vitro, and an AQP1 inhibitor was used to examine whether AQP1 could promote M1 polarization and pyroptosis in response to LPS. Transcriptome and cell experiments showed that this effect was related to a decrease in chemokines caused by AQP1 deficiency. AQP1 participates in M1 polarization and pyroptosis in macrophages by increasing the levels of chemokines induced by LPS, which provides new insights for the diagnosis and treatment of ALI.
摘要：
急性呼吸道感染（ARIs）与高死亡率和高发病率相关。急性肺损伤（ALI）是由SARS-CoV-2等病毒引起的ARI过程中免疫细胞的激活引起的。水通道蛋白1（AQP1）分布在多种免疫细胞中，与ALI的发生有关，但机制尚不清楚。人类单细胞的参考图谱用于在单细胞水平上识别COVID-19患者的巨噬细胞。“FindMarkers”用于分析差异表达基因(DEGs)，和“clusterProfiler”用于分析DEG的功能。用脂多糖(LPS)体外建立M1巨噬细胞极化模型,并使用AQP1抑制剂检查AQP1，焦亡和M1极化之间的关系。转录组测序和RT-qPCR用于研究AQP1调节巨噬细胞极化和焦亡的分子机制。抗原呈递，M1极化，在SARS-CoV-2感染的巨噬细胞中迁移和吞噬作用异常，这与AQP1的高表达有关。体外构建了巨噬细胞M1极化模型,并使用AQP1抑制剂来检查AQP1是否可以促进响应LPS的M1极化和焦亡。转录组和细胞实验表明，这种作用与AQP1缺乏引起的趋化因子减少有关。AQP1通过增加LPS诱导的趋化因子水平参与巨噬细胞的M1极化和焦亡，为ALI的诊断和治疗提供了新的见解。
