Meiqi Sun , Hua Fang , Jiashu Zhang , Mengyao Wang , Peng Jiang , LiLi Ma , Huanyu Jin , Wei Zhang
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引用次数: 0
Abstract
Silicosis is a fatal occupational lung disease characterized by persistent inflammation and irreversible fibrosis. However, the pathogenesis of silicosis is currently unclear. In this study, a mouse model of silicosis was established by intranasal instillation of silica, and transcriptomic alterations in lung tissues were assessed by mRNA-sequencing. Cholesterol 25-hydroxylase (Ch25h) was upregulated in silicotic lung tissues and alveolar macrophages. Lentivirus-mediated Ch25h knockdown was then employed to assess its functional role in vivo. It was found that Ch25h knockdown alleviated associated pathological changes, including pulmonary injury and fibrosis. Additionally, Ch25h significantly modulated NLRP3 inflammasome activity in vivo and in vitro. Knockdown of Ch25h inhibited the secretion of inflammatory factor (IL-1α, IL-1β, and IL-18), decreased the protein level of cleaved caspase-1 and GSDMD-N in macrophages, and reduced potassium ion efflux and lactate dehydrogenase (LDH) release. Notably, ASC (apoptosis-related spotted protein) oligomerization was suppressed by Ch25h downregulation, suggesting that Ch25h was required for the inflammasome assembly. Our findings suggest that Ch25h may contribute to silicosis development by regulating NLRP3 inflammasome activation and pyroptosis, warranting further investigation as a possible therapeutic target.
期刊介绍:
IJBCB publishes original research articles, invited reviews and in-focus articles in all areas of cell and molecular biology and biomedical research.
Topics of interest include, but are not limited to:
-Mechanistic studies of cells, cell organelles, sub-cellular molecular pathways and metabolism
-Novel insights into disease pathogenesis
-Nanotechnology with implication to biological and medical processes
-Genomics and bioinformatics