Importance of Selenoprotein O in Regulating Hmgb1: A New Direction for Modulating ROS-Dependent NETs Formation to Aggravate the Progression of Acute Liver Inflammation

作者：Xia Yu, Kai Chen, Yidan Wang, Qihang Jiang, Yongzhen Du, Dongliu Luo, Xiang Li, Shu Li · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.5c01956 · 被引用次数：5 · 研究领域：Advanced Glycation End Products research、Heme Oxygenase-1 and Carbon Monoxide、Biomedical Research and Pathophysiology

Selenoproteins (Sels) are a class of essential biomolecules that play critical roles in cellular homeostasis. SelO was identified as the preferential source of selenium in the liver, implying its potential as a key regulatory factor in hepatic pathophysiology. Bioinformatics analysis of data from GEO data sets revealed marked downregulation of SelO in liver injury. However, its function and regulatory mechanisms in the liver remain unclear. To address this, we investigated the effect of SelO ablation on acute liver inflammation, focusing on its association with inflammation and neutrophil extracellular traps (NETs) formation. Wild-type (WT) and SelO -knockout mice were used to establish a lipopolysaccharide (LPS) exposure model and a coculture model (AML12 cells and neutrophils) in vitro. Our findings revealed that LPS stimulation significantly reduced SelO expression in the WT mouse liver. SelO deletion promoted the expression of Hmgb1 and marker cytokines for chemokines, NETs generation, pyroptosis and inflammation, and induced an imbalance in redox homeostasis. Immunofluorescence, SYTOX staining, and scanning electron microscopy confirmed that SelO silencing promoted reactive oxygen species (ROS)-dependent NETs formation. Moreover, the coculture model demonstrated that excessive NETs formation exacerbated SelO -ablation-induced hepatic inflammation. Importantly, we confirmed the significant involvement of the Hmgb1/ROS axis in the development of acute liver inflammation in...