霍洛石纳米管和多壁碳纳米管对静脉注射后小鼠心脏中克鲁珀尔样因子 15 介导的下游事件的影响

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Cardiovascular Toxicology Pub Date : 2024-04-01 Epub Date: 2024-02-27 DOI:10.1007/s12012-024-09844-7
Yimin Zhang, Yujia Cheng, Weichao Zhao, Fengmei Song, Yi Cao
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引用次数: 0

摘要

霍洛石纳米管(HNTs)是一种从天然粘土中提取的纳米材料(NMs),一直被认为是生物医学用途的生物相容性 NMs。然而,HNTs 的心血管毒性尚未得到深入研究。在这项研究中,我们比较了 HNTs 和多壁碳纳米管(MWCNTs)的心脏毒性,重点研究了 Kruppel 样因子(KLF)介导的信号通路的变化。小鼠静脉注射 50 µg NMs,每天一次,连续 5 天,然后取出小鼠心脏进行实验。虽然 HNTs 或 MWCNTs 没有诱发明显的病理变化,但 RNA 序列数据表明 KLF 基因表达发生了改变。我们进一步证实了 Klf15 阳性细胞的增加,以及与 Klf15 相关的基因本体(GO)术语的变化。我们注意到,GO术语的变化大多与基因表达调控有关。我们证实,NMs增加了myoneurin(Mynn),但减少了蜗牛家族转录抑制因子1(Snai1),这两个转录因子(TFs)与Klf15有关。此外,改变的 GO 术语还包括金属离子结合和葡萄糖输入的正调控,我们还验证了磷酸烯醇丙酮酸羧激酶 1(Pck1)和胰岛素受体(Insr)的增加。然而,HNTs 和 MWCNTs 对细胞死亡信号通路的影响微乎其微,并且在 NM 处理后未观察到凋亡位点的增加。我们的结论是,静脉注射 HNTs 和 MWCNTs 激活了一种保护性 TF,即小鼠主动脉中的 Klf15,从而改变了与金属离子结合和葡萄糖输入相关的基因表达和信号通路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Effects of Halloysite Nanotubes and Multi-walled Carbon Nanotubes on Kruppel-like Factor 15-Mediated Downstream Events in Mouse Hearts After Intravenous Injection.

Effects of Halloysite Nanotubes and Multi-walled Carbon Nanotubes on Kruppel-like Factor 15-Mediated Downstream Events in Mouse Hearts After Intravenous Injection.

Halloysite nanotubes (HNTs) are nanomaterials (NMs) derived from natural clays and have been considered as biocompatible NMs for biomedical uses. However, the cardiovascular toxicity of HNTs has not been thoroughly investigated. In this study, we compared the cardiotoxicity of HNTs and multi-walled carbon nanotubes (MWCNTs), focusing on the changes in Kruppel-like factor (KLF)-mediated signaling pathways. Mice were intravenously injected with 50 µg NMs, once a day, for 5 days, and then mouse hearts were removed for experiments. While HNTs or MWCNTs did not induce obvious pathological changes, RNA-sequencing data suggested the alterations of KLF gene expression. We further confirmed an increase of Klf15 positive cells, accompanied by changes in Klf15-related gene ontology (GO) terms. We noticed that most of the changed GO terms are related with the regulation of gene expression, and we confirmed that the NMs increased myoneurin (Mynn) but decreased snail family transcriptional repressor 1 (Snai1), two transcription factors (TFs) related with Klf15. Besides, the changed GO terms also include metal ion binding and positive regulation of glucose import, and we verified an increase of phosphoenolpyruvate carboxykinase 1 (Pck1) and insulin receptor (Insr). However, HNTs and MWCNTs only showed minimal impact on cell death signaling pathways, and no increase in apoptotic sites was observed after NM treatment. We concluded that intravenous administration of HNTs and MWCNTs activated a protective TF, namely Klf15 in mouse aortas, to alter gene expression and signaling pathways related with metal ion binding and glucose import.

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来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
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