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 

作者机构：Department of Occupational Health and Environmental HealthSchool of Public Health and Beijing Key Laboratory of Environmental ToxicologyCapital Medical UniversityBeijing 100069China Beijing Key Laboratory of Environmental ToxicologyCapital Medical UniversityBeijing 100069China Department of Toxicology and Sanitary ChemistrySchool of Public HealthCapital Medical UniversityBeijing 100069China 

出 版 物：《Environment & Health》 (环境与健康（英文）)

年 卷 期：2024年第2卷第11期

页      面：786-801页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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) 

主　　题：silica nanoparticles single-cell RNA-Seq lung toxicity lung interstitial disease proteostasis 

摘      要：The adverse respiratory outcomes motivated by silica nanoparticles(SiNPs)exposure have received increasing ***,we aim to elucidate the interplay of diverse cell populations in the lungs and key contributors in triggering lung injuries caused by *** 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 *** revealed that SiNPs caused pulmonary interstitial injury in rats by histopatho-logical examination and pulmonary hydroxyproline ***,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 *** 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 *** cell-specific responses may serve a synergistic role in the pathogenesis of pulmonary interstitial disease triggered by *** 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 *** 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 *** together,our study provides insights into pulmonary toxic effects and underlying molecular mechanisms of SiNPs from a single-cell perspective.