Profiling gene expression reveals insights into pulmonary response to aerosolized botulinum toxin type A exposure in mice

Su Duo; Gan Changjiao; Jiao ZhouguangDeng MengyunLi ShaJu YingjiaoQiu YefengHu LingfeiGao BoZhou DongshengZhao YueeYang Huiying

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Profiling gene expression reveals insights into pulmonary response to aerosolized botulinum toxin type A exposure in mice

机译：Profiling gene expression reveals insights into pulmonary response to aerosolized botulinum toxin type A exposure in mice

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Botulinum neurotoxin type A (BoNT/A) is traditional medicine and well known for its therapeutic use as an anesthetic and in cosmetic applications that work through the inhibition of acetylcholine exocytosis in neuronal cells. BoNT/A also has the potential to function as a biological weapon due to its high mortality rate and ease of dispersal. Emerging evidence suggests that BoNT/A exhibits biological effects on nonneuronal cells. In cytology experiments, BoNT/A induces global gene expression alterations. However, pulmonary effects from exposure to aerosolized BoNT/A have not been evaluated. This study investigated the global transcriptional profile of lung tissues after botulism inhalation. A mice model of inhaled botulism was established using intratracheal exposure to aerosolized BoNT/A and described through histological examination and flow cytometry. Transcriptomic analysis revealed that genes related to acute inflammatory responses were upregulated at 12-h postexposure. Increased expression of multiple anti-inflammatory marker genes and decreased expression of pro-inflammatory marker genes were observed at 48- to 72-h postexposure, underscoring a transcriptional shift toward a pro-reparative phenotype. Histological examination and cell proportions analysis mirrored these expression patterns. Accordingly, the orchestration of a quick phenotype transition prompted by BoNT/A may have the potential for promoting the resolution of the inflammatory lung. To our knowledge, this study represents the first research to investigate the pulmonary transcriptional responses of aerosolized BoNT/A exposure; the results may provide new insights in elucidating the molecular mechanism for pulmonary inhaled botulism and highlight the potential therapeutic application of BoNT/A in mitigating inflammatory conditions.

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来源
《Journal of applied toxicology》 |2021年第10期|1479-1490|共12页
作者
Su Duo; Gan Changjiao; Jiao ZhouguangDeng MengyunLi ShaJu YingjiaoQiu YefengHu LingfeiGao BoZhou DongshengZhao YueeYang Huiying;
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作者单位

Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 10071, Peoples R;

Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genome Sci & Informat, Beijing, Peoples R China;

Acad Mil Med Sci, Lab Anim Ctr, Beijing, Peoples R China;

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正文语种英语
中图分类毒物学（毒理学）;
关键词
botulinum neurotoxin type A; molecular pathology; pulmonary inhaled botulism; resolution of inflammation; RNA sequencing;

Profiling gene expression reveals insights into pulmonary response to aerosolized botulinum toxin type A exposure in mice

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