Neutrophil extracellular traps-triggered impaired autophagic flux via METTL3 underlies sepsis-associated acute lung injury

Neutrophil extracellular traps (NETs) assist pathogen clearance, while excessive NETs formation is associated with exacerbated inflammatory responses and tissue injury in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Autophagy is generally considered to be a protective process,...

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Published in:Cell death discovery 2022-08, Vol.8 (1), p.375-375, Article 375
Main Authors: Qu, Mengdi, Chen, Zhaoyuan, Qiu, Zhiyun, Nan, Ke, Wang, Yanghanzhao, Shi, Yuxin, Shao, Yuwen, Zhong, Ziwen, Zhu, Shuainan, Guo, Kefang, Chen, Wankun, Lu, Xihua, Wang, Zhiping, Zhang, Hao, Miao, Changhong
Format: Article
Language:English
Subjects:
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Alveoli
Anesthesiology
Animal models
Apoptosis
Autophagy
Biochemistry
Biomedical and Life Sciences
Cancer
Cell Biology
Cell Cycle Analysis
Cytokines
DNA methylation
Epithelial cells
Hospitals
Inflammation
Leukocytes (neutrophilic)
Life Sciences
Lungs
Methylation
Microscopy
mRNA
N6-methyladenosine
Neutrophils
Patients
Plasma
Respiratory distress syndrome
Sepsis
SIRT1 protein
Stem Cells
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Summary:Neutrophil extracellular traps (NETs) assist pathogen clearance, while excessive NETs formation is associated with exacerbated inflammatory responses and tissue injury in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Autophagy is generally considered to be a protective process, but autophagy dysfunction is harmful. Whether and how NETs affect autophagic flux during sepsis-induced ALI are currently unknown. Here, we confirmed that the level of NETs was increased in ARDS patients and mice models, which led to impairment of autophagic flux and deterioration of the disease. Mechanistically, NETs activated METTL3 mediated m 6 A methylation of Sirt1 mRNA in alveolar epithelial cells, resulting in abnormal autophagy. These findings provide new insights into how NETs contribute to the development of sepsis-associated ALI/ARDS.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-022-01166-3