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Inhibition of VNN1-Induced ROS-Dependent NETs Formation Alleviates Lung Injury and Systemic Inflammation in Sepsis
Shishuai Meng1, Xinyue Ma1, Wei Yang1
1Department of Intensive Care Unit, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People's Republic of China.
Journal of Inflammation Research
|July 20, 2026
Summary
Vascular non-inflammatory molecule 1 (VNN1) drives neutrophil extracellular traps (NETs) formation in sepsis. Inhibiting VNN1 reduces NETs, mitigating lung injury and inflammation in septic mice.
Area of Science:
- Immunology
- Pathophysiology
- Molecular Biology
Background:
- Excessive neutrophil extracellular traps (NETs) formation exacerbates sepsis progression.
- Vascular non-inflammatory molecule 1 (VNN1) is a glycosylphosphatidylinositol-anchored protein implicated in inflammatory processes.
Purpose of the Study:
- To investigate the mechanism by which VNN1 influences NETs formation.
- To explore the role of VNN1 in sepsis pathogenesis and potential therapeutic inhibition.
Main Methods:
- Isolation of mouse bone marrow neutrophils and mRNA sequencing.
- Establishment of a cecum ligation and puncture-induced sepsis mouse model.
- Utilized histopathology, PCR, ELISA, flow cytometry, and Western blot for phenotypic analysis.
Main Results:
- VNN1 induced reactive oxygen species (ROS)-dependent NETs formation in vitro.
- S100A9 elevated VNN1 levels, promoting NET formation via VNN1.
- In vivo VNN1 inhibition ameliorated lung injury and systemic inflammation in septic mice by reducing NETs.
Conclusions:
- S100A9 enhances VNN1 protein levels, driving VNN1-dependent NETs formation.
- VNN1 inhibition, using PFI-653, suppresses NADPH oxidase-derived ROS and NETs formation.
- Inhibition of VNN1 offers a potential therapeutic strategy for sepsis by reducing lung injury and inflammation.