Lung Single-Cell Transcriptomics Offers Insights into the Pulmonary Interstitial Toxicity Caused by Silica Nanoparticles  

作　　者：Yan Li Qing Yao Hailin Xu Jiaze Ren Yurou Zhu Caixia Guo Yanbo Li 

机构地区：[1]Department of Occupational Health and Environmental Health,School of Public Health and Beijing Key Laboratory of Environmental Toxicology,Capital Medical University,Beijing 100069,China [2]Beijing Key Laboratory of Environmental Toxicology,Capital Medical University,Beijing 100069,China [3]Department of Toxicology and Sanitary Chemistry,School of Public Health,Capital Medical University,Beijing 100069,China

出　　处：《Environment & Health》2024年第11期786-801,共16页环境与健康（英文）

基　　金：supported by the National Natural Science Foundation of China(82273658,82173551);Special Funds for the Construction of High-level Public Health Technical Talents(xuekegugan-01-048).

摘　　要：The adverse respiratory outcomes motivated by silica nanoparticles(SiNPs)exposure have received increasing attention.Herein,we aim to elucidate the interplay of diverse cell populations in the lungs and key contributors in triggering lung injuries caused by SiNPs.We conducted a subchronic respiratory exposure model of SiNPs via intratracheal instillation in Wistar rats,where rats were administered with 1.5,3.0,or 6.0 mg/kg body weight SiNPs once a week for 12 times in total.We revealed that SiNPs caused pulmonary interstitial injury in rats by histopatho-logical examination and pulmonary hydroxyproline determination.Further,a single-cell RNA-Seq via screening 10457 cells in the rat lungs disclosed cell-specific responses to SiNPs and cell-to-cell interactions within the alveolar macrophages,epithelial cells,and fibroblasts from rat lungs.These disturbed responses were principally related to the dysregulation of protein homeostasis(proteostasis),accompanied by an inflammatory response in macrophages,cell death in epithelial,proliferation,and extracellular matrix deposition in fibroblast.These cell-specific responses may serve a synergistic role in the pathogenesis of pulmonary interstitial disease triggered by SiNPs.In particular,the analyses of gene interaction networks and gene−disease associations filtered out heat shock proteins(Hsps)family genes crucial to the observed pulmonary lesions caused by SiNPs.Of note,both GEO database analysis and our experiments’validation indicated that Hsps,especially Hspd1,may be a key contributor to pulmonary interstitial injury,possibly through triggering oxidative stress,immune response,and disrupting protein homeostasis.Taken together,our study provides insights into pulmonary toxic effects and underlying molecular mechanisms of SiNPs from a single-cell perspective.

关 键 词：silica nanoparticles single-cell RNA-Seq lung toxicity lung interstitial disease PROTEOSTASIS 

分 类 号：R12[医药卫生—环境卫生学]