Single-cell Transcriptomics Reveals Predominantly Inflammatory Endothelial Cell Responses and Suppressed Vascular Repair in Silicosis

Dongli Cao^1,2Huashun Cui³Zequan Chen³Heyang Li³Bing Li^2,3Jianhua Wang^1,2*

• ¹Anhui University of Science and Technology, Huainan, China
• ²Anhui Province Engineering Laboratory of Occupational Health and Safety, Huainan, China
• ³Anhui University of Science and Technology School of Medicine, Huainan, China

Silicosis is a progressive fibrotic lung disease without effective treatment options, and its pathogenesis remains incompletely understood, particularly the role of endothelial cells (ECs). Here, we utilized single-cell RNA sequencing to characterize endothelial responses in lungs from silica-exposed mice. We identified two functionally distinct endothelial subpopulations: an inflammatory EC subtype exhibiting significantly increased abundance, characterized by high expression of neutrophilrecruiting factors such as Spp1 (osteopontin), CCL (C-C motif chemokine ligand), and the ESAM(endothelial cell-selective adhesion molecule), suggesting active involvement in promoting neutrophil influx and persistent inflammation; and 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. 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.