2. Academic Validation
  3. GSDMD promotes neutrophil extracellular traps via mtDNA-cGAS-STING pathway during lung ischemia/reperfusion

GSDMD promotes neutrophil extracellular traps via mtDNA-cGAS-STING pathway during lung ischemia/reperfusion

  • Cell Death Discov. 2023 Oct 4;9(1):368. doi: 10.1038/s41420-023-01663-z.
Chen Zhao # 1 2 3 4,  Fangte Liang # 1 2 3 4,  Mengling Ye 5,  Siyi Wu 1 2 3 4,  Yi Qin 1 2 3 4,  Lu Zhao 1 2 3 4,  Lu Zhang 1 2 3 4,  Jing He 1 2 3 4,  Liming Cen 1 2 3 4,  Fei Lin 6 7 8 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China.
  • 2 Guangxi Clinical Research Center for Anesthesiology, Nanning, China.
  • 3 Guangxi Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Nanning, China.
  • 4 Guangxi Health Commission Key Laboratory of Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, China.
  • 5 Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China.
  • 6 Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China. linfei@gxmu.edu.cn.
  • 7 Guangxi Clinical Research Center for Anesthesiology, Nanning, China. linfei@gxmu.edu.cn.
  • 8 Guangxi Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Nanning, China. linfei@gxmu.edu.cn.
  • 9 Guangxi Health Commission Key Laboratory of Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, China. linfei@gxmu.edu.cn.
  • # Contributed equally.
PMID: 37794018 DOI: 10.1038/s41420-023-01663-z
Abstract

Lung ischemia/reperfusion injury (LIRI) is a complex pathophysiological process, with the histopathological hallmark of neutrophils migrating into the lungs. Neutrophil extracellular traps (NETs) have been suggested to exert a critical role in the pathogenesis of inflammation and Infection in humans and Animals, while the exact functions and underlying mechanisms of NETs in LIRI remain insufficiently elucidated. In this study, we investigated the role of pore-forming protein gasdermin D (GSDMD) on NETs release in LIRI induced by lung ischemia/reperfusion (I/R). We found that disulfiram, a GSDMD inhibitor, dramatically reduced NETs release and pathological injury in lung I/R in vivo and in vitro. Additionally, GSDMD caused mitochondrial DNA (mtDNA) leaking into the neutrophil cytosol, and then the cytoplasmic mtDNA activated the cGAS-STING signaling pathway and stimulated NETs formation in lung I/R. Furthermore, inhibition of cGAS/STING pathway could inhibit cytosol mtDNA mediated NETs formation.

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