纳米银诱导细胞毒性从基因到代谢物水平的分子机制研究。

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-07-24 DOI:10.1038/s41598-025-12477-7

Yan Huang, Rong Chen, Ye Chen, Xiaoying Lü

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引用次数: 0

摘要

本研究的目的是通过对转录组学和代谢组学结果的综合分析，从基因到代谢物水平探索银纳米颗粒（AgNP）诱导细胞毒性的机制。首先，转录组测序技术显示，暴露于银纳米颗粒4、8和24小时后，1365、1241和2790个基因在人真皮成纤维细胞（HDFs）中差异表达，涉及250、248和280条生物学途径。然后通过代谢组学结果对比，发现7条代谢途径（嘌呤代谢途径、甘油磷脂代谢途径等），9个上游关键基因（ADCY4、SPHK1等）和8个下游代谢物（黄嘌呤、胆碱等）共同参与agnp诱导的细胞毒性。最后，验证实验结果表明AgNPs通过这些途径发挥毒性作用，诱导氧化应激、影响能量代谢、阻滞细胞周期、破坏细胞骨架、抑制细胞增殖、触发细胞凋亡。

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Investigation of molecular mechanisms in silver nanoparticle-induced cytotoxicity from gene to metabolite level.

The aim of this study was to explore the mechanisms in silver nanoparticle (AgNP)-induced cytotoxicity from gene to metabolite levels through an integrative analysis of transcriptomics and metabolomics results. First, transcriptome sequencing technology revealed 1365, 1241, and 2790 genes differentially expressed within human dermal fibroblasts (HDFs) after 4, 8, and 24 h of exposure to silver nanoparticles, which were involved in 250, 248, and 280 biological pathways. Then, by comparing with the metabolomics results, 7 metabolic pathways (purine metabolism pathway, glycerophospholipid metabolism pathway, etc.), with 9 key upstream genes (ADCY4, SPHK1, etc.) and 8 downstream metabolites (xanthine, choline, etc.) jointly involved were found relate to AgNP-induced cytotoxicity. Finally, the results of the validation experiments revealed that AgNPs exerted the toxic effects through these pathways, inducing oxidative stress, affecting energy metabolism, arresting the cell cycle, disrupting the cytoskeleton, inhibiting cell proliferation, and triggering apoptosis.

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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