2. Academic Validation
  3. Neutrophil extracellular traps-triggered impaired autophagic flux via METTL3 underlies sepsis-associated acute lung injury

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

  • Cell Death Discov. 2022 Aug 27;8(1):375. doi: 10.1038/s41420-022-01166-3.
Mengdi Qu 1 2,  Zhaoyuan Chen 1 2,  Zhiyun Qiu 1 2,  Ke Nan 1 2,  Yanghanzhao Wang 1 2,  Yuxin Shi 1 2,  Yuwen Shao 1 2,  Ziwen Zhong 1 2,  Shuainan Zhu 1 2,  Kefang Guo 1 2,  Wankun Chen 1 2,  Xihua Lu 3,  Zhiping Wang 4,  Hao Zhang 5 6,  Changhong Miao 7 8 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Zhongshan Hospital, Fudan University; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, China.
  • 3 Department of Anesthesiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
  • 4 Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. zhpsqxt@126.com.
  • 5 Department of Anesthesiology, Zhongshan Hospital, Fudan University; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. fuscc_anesthesia@yeah.net.
  • 6 Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, China. fuscc_anesthesia@yeah.net.
  • 7 Department of Anesthesiology, Zhongshan Hospital, Fudan University; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. miaochangh@163.com.
  • 8 Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, China. miaochangh@163.com.
  • 9 Department of Anesthesiology, Jinshan Hospital, Fudan University, Shanghai, China. miaochangh@163.com.
PMID: 36030287 DOI: 10.1038/s41420-022-01166-3
Abstract

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 m6A 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.

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