Introduction Silicosis is a progressive fibrotic lung disease without effective treatment options, and its pathogenesis remains incompletely understood, particularly the role of endothelial cells (ECs). Methods Here, we utilized single-cell RNA sequencing to characterize endothelial responses in lungs from silica-exposed mice. Results We identified two functionally distinct endothelial subpopulations: 1. An inflammatory EC subtype, exhibiting significantly increased abundance and characterized by high expression of neutrophil-recruiting factors such as Spp1 (osteopontin), CCL (C-C motif chemokine ligand), and ESAM (endothelial cell–selective adhesion molecule), suggesting active involvement in neutrophil influx and persistent inflammation. 2. A reparative EC subtype, marked by upregulation of angiogenesis and vascular repair pathways, which exhibited decreased abundance and functional suppression within the silicotic lung microenvironment. Discussion These results indicate a pathological shift toward inflammation-amplifying endothelial cells and impaired reparative capacity during silicosis progression. Our findings provide new mechanistic insights into endothelial cell dysfunction in silicosis and highlight potential targets for therapeutic intervention.
Cao et al. (Wed,) studied this question.