Yan Huang, Fudan Zhang, Yajing Zhang, Rong Chen, Xiaoying Lü
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引用次数: 0
摘要
生物标志物因其优势已被应用于生物材料的毒性评估。然而,生物材料生物标志物的研究仍处于早期阶段。生物标志物研究缺乏基于多组学研究的综合分析。在此,我们报告了一种结合基因/蛋白质和代谢物多组学揭示镍离子(Ni2+)细胞毒性生物标志物及其内在机制的新方法。首先,比较差异表达的基因和蛋白质,筛选出在相同的镍2+处理组中表现出一致差异表达的基因/蛋白质对。接着,进行了代谢通路分析,以揭示基因/蛋白对和代谢物显示上游和下游关系的通路。随后确定了由基因/蛋白对、代谢物和代谢途径以及候选生物标记物组成的重要网络。通过表达水平和功能验证,确认了基因/蛋白质/代谢物生物标记物,并揭示了其潜在机制:Ni2+影响了Rrm2基因生物标志物的表达,进而影响了RRM2蛋白生物标志物的表达。这些变化反过来又影响了尿酸和尿苷代谢物生物标志物的水平,最终抑制了 DNA 合成,抑制了细胞增殖,增加了细胞内 ROS 水平并降低了 ATP 含量。
Combination of gene/protein and metabolite multiomics to reveal biomarkers of nickel ion cytotoxicity and the underlying mechanism.
Biomarkers have been applied for toxicity assessment of biomaterials due to their advantages. However, research on biomarkers for biomaterials is still in its early stages. There is a lack of integrated analysis in biomarker research based on multiomics studies. Herein, we report a new approach for combining of gene/protein and metabolite multiomics to reveal biomarkers of nickel ion (Ni2+) cytotoxicity and the underlying mechanism. Firstly, differentially expressed genes and proteins were compared to screen gene/protein pairs exhibiting consistent differential expression within the same Ni2+-treated groups. Next, metabolic pathway analysis was carried out to reveal pathways in which gene/protein pairs and metabolites showed upstream and downstream relationships. Important networks composed of gene/protein pairs, metabolites and metabolic pathways and candidate biomarkers were subsequently identified. Through expression level and function validation, the gene/protein/metabolite biomarkers were confirmed, and the underlying mechanism was revealed: Ni2+ influenced the expression of the Rrm2 gene biomarker, which subsequently affected the expression of the RRM2 protein biomarker. These changes in turn impacted the levels of uric acid and uridine metabolite biomarkers, ultimately inhibiting DNA synthesis, suppressing cell proliferation, increasing intracellular ROS levels and reducing ATP content.
期刊介绍:
Regenerative Biomaterials is an international, interdisciplinary, peer-reviewed journal publishing the latest advances in biomaterials and regenerative medicine. The journal provides a forum for the publication of original research papers, reviews, clinical case reports, and commentaries on the topics relevant to the development of advanced regenerative biomaterials concerning novel regenerative technologies and therapeutic approaches for the regeneration and repair of damaged tissues and organs. The interactions of biomaterials with cells and tissue, especially with stem cells, will be of particular focus.