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石墨化多壁碳纳米管引起的肺部炎症和纤维发生反应涉及 cGAS-STING 信号通路。

Pulmonary inflammatory and fibrogenic response induced by graphitized multi-walled carbon nanotube involved in cGAS-STING signaling pathway.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China.

出版信息

J Hazard Mater. 2021 Sep 5;417:125984. doi: 10.1016/j.jhazmat.2021.125984. Epub 2021 May 4.

DOI:10.1016/j.jhazmat.2021.125984
PMID:34020360
Abstract

Graphitized multi-walled carbon nanotubes (GMWCNTs) are a new type of nanomaterial. Recently, their production and application in biological medicine have grown rapidly. However, GMWCNTs may cause adverse health effects, including the common occupational disease of pulmonary fibrosis. Pulmonary fibrosis is a serious progressive disease that often leads to lung failure, high mortality, and disability, and there is no effective therapy currently available. Therefore, identifying new biomarkers of the disease is important to better understand the disease mechanisms and explore new therapeutic strategies. In this study, 40 μg of GMWCNTs was used to treat mice in vivo by pharyngeal aspiration, and different genes were screened by transcriptome sequencing. Activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signal pathway had an important effect on the development of pulmonary inflammation and fibrosis. GMWCNTs were then administered to the mice with a STING inhibitor (C-176). Inhibition of STING effectively decreased pulmonary inflammation and fibrosis in mice induced by GMWCNTs. Collectively, activation of the cGAS-STING signaling pathway is involved in GMWCNT-induced pulmonary inflammation and fibrosis in mice.

摘要

石墨化多壁碳纳米管(GMWCNTs)是一种新型纳米材料。最近,它们在生物医学中的生产和应用迅速发展。然而,GMWCNTs 可能会引起不良的健康影响,包括常见的职业性肺纤维化。肺纤维化是一种严重的进行性疾病,常导致肺衰竭、高死亡率和残疾,目前尚无有效的治疗方法。因此,鉴定疾病的新生物标志物对于更好地了解疾病机制和探索新的治疗策略非常重要。在这项研究中,通过咽吸入将 40μg 的 GMWCNTs 用于体内处理小鼠,并通过转录组测序筛选出不同的基因。环鸟苷酸-腺苷酸合成酶(cGAS)-干扰素基因刺激物(STING)信号通路的激活对肺炎症和纤维化的发展有重要影响。然后,将 GMWCNTs 给予具有 STING 抑制剂(C-176)的小鼠。STING 的抑制作用有效地降低了 GMWCNTs 诱导的小鼠肺部炎症和纤维化。总之,cGAS-STING 信号通路的激活参与了 GMWCNT 诱导的小鼠肺部炎症和纤维化。

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