Metabolic landscape of human alveolar type II epithelial cells undergoing epithelial-mesenchymal transition induced directly by silica exposure  

作　　者：Jin Sun Na Zhao Ruijia Zhang Yizheng Li Tiantian Yu Qiying Nong Li Lin Xubin Yang Tiangang Luan Baowei Chen Yongshun Huang 

机构地区：[1]Southern Marine Science and Engineering Guangdong Laboratory,School of Marine Sciences,Sun Yat-Sen University,Zhuhai 519082,China [2]Guangdong Province Hospital for Occupational Disease Prevention and Treatment,Guangzhou 510300,China [3]Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center,Jieyang 515200,China [4]State Key Lab of Bioresource and Biocontrol,School of Life Science,Sun Yat-sen University,Guangzhou 510275,China [5]Metabolic Innovation Center,Zhongshan School of Medicine,Sun Yat-Sen University,Guangzhou 540080,China [6]Department of Endocrinology and Metabolism,Guangdong Provincial Key Laboratory of Diabetology,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510630,China

出　　处：《Journal of Environmental Sciences》2025年第3期676-687,共12页环境科学学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(Nos.22206207,22127810,and 22276224);the Natural Science Foundation of Guangdong Province(Nos.2021A1515011546 and 2023A1515010085);the Science and Technology Planning Project of Guangzhou(No.202102080005)。

摘　　要：Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.

关 键 词：Silica exposure Human alveolar type II epithelial cells(ATII cells) Epithelial-mesenchymal transition(EMT) Metabolomics GLUTAMINE 

分 类 号：R73[医药卫生—肿瘤]