Integrated high-throughput small RNA and transcriptome sequencing unveil the shape-dependent toxicity of nano-alumina in rat astrocytes

Environmental Sciences Europe

Li Dong¹  Fuchang Deng¹  Yuanzheng Fu¹  Yuanyuan Chen¹  Mu Zhu¹  Yaqiang Cao²  Song Tang²  Dayna Schultz³  Kamran Shekh⁴  Guangqiu Qin⁵ 

[1] China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan Nanli, Chaoyang District, 100021, Beijing, China;China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan Nanli, Chaoyang District, 100021, Beijing, China;Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, Jiangsu, China;Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece;Department of Physiology, University of Alberta, Edmonton, Canada;Department of Preventive Medicine, Guangxi University of Chinese Medicine, 530200, Nanning, Guangxi, China;

关键词: Nanoparticles;    Morphology;    High-throughput sequencing;    MicroRNAs;    Transcriptome;    Pathway analysis;   

DOI  :  10.1186/s12302-021-00540-9

来源: Springer

【 摘 要 】

BackgroundThe large-scale applications of alumina nanoparticles (Al2O3-NPs), one of the most important NPs in the global market, are causing severe damages to the environment and human health. Our previous research has revealed a critical role of nanoparticle morphology (e.g., flake and rod) in determining the toxic potencies of Al2O3-NPs, where nanorods demonstrated a significantly stronger toxic response than that of nanoflakes. However, their underlying mechanisms have not been completely elucidated yet. In the present study, we evaluated and compared the potential toxicological mechanisms of two shapes of γ-Al2O3-NPs (flake versus rod) by measuring miRNA and mRNA profiles of astrocytes in rat cerebral cortex, ex vivo.ResultsA total of 269 mRNAs and 122 miRNAs, 180 mRNAs and 116 miRNAs were differentially expressed after nanoflakes or nanorods exposure, respectively. Among them, 55 miRNAs (e.g., miR-760-5p, miR-326-3p, and miR-35) and 105 mRNAs (e.g., Kdm4d, Wdr62, and Rps6) showed the same trend between the two shapes. These miRNAs and mRNAs were mainly involved in apoptosis, inflammatory pathways (e.g., NF-kappa B), carcinogenic pathways (e.g., MAPK, p53, Notch, Rap1, and Ras), and cellular lipid metabolisms (e.g., glycerolipid metabolism, sphingolipid, and ether lipid metabolism). However, the remaining miRNAs and mRNAs either showed an opposite trend or only changed by a particular shape. Nanorods could specifically alter the changes of PI3K/Akt, AMPK and TNF pathways, cell cycle, and cellular senescence, while nanoflakes caused the changes of Toll and lmd signaling pathways.ConclusionsCombined with previous research results, we further revealed the potential biomolecular mechanisms leading to the stronger toxicity of nanorods than that of nanoflakes, and multi-omics is a powerful approach to elucidate morphology-related mode of actions.

【 授权许可】

CC BY