通过miR-26a-5p/PTEN途径,huc - msc来源的外泌体减轻了铅对人神经母细胞瘤细胞的毒性。

IF 3.9 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Food and Chemical Toxicology Pub Date : 2025-02-01 DOI:10.1016/j.fct.2024.115177
Yiren Xiong , Jiayi He , Shanshan He , Zuqing Hu , Di Ouyang , Renyi Liu , Zhenjie Gao , Weiguang Zhang , Zhujun Kang , Shuyi Lan , Yang Wang , Fatoumata Diallo , Dalin Hu
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引用次数: 0

摘要

铅是一种普遍存在的环境化学物质,对人体有多种毒性损害。本研究旨在探讨人脐带间充质干细胞衍生外泌体(HUC-MSC-exo)对铅神经毒性的干预作用及其机制。采用差梯度超离心分离HUC-MSC-exo。采用纳米颗粒追踪法(NTA)、透射电镜(TEM)技术和外泌体特异性生物标志物CD9、CD63和CD81进行外泌体鉴定。受体细胞为人神经母细胞瘤细胞(SH-SY5Y)。共聚焦激光扫描显微镜分析证实SH-SY5Y细胞摄取HUC-MSC-exo。分析细胞迁移能力、凋亡、IL-6、IL-1β、TNF-α。评估miR-26a-5p/PTEN轴的作用。结果表明,SH-SY5Y细胞暴露铅后,miR-26a-5p/PTEN通路被激活,miR-26a-5p表达下调,PTEN表达上调,与对照组相比,细胞迁移明显减少,凋亡增加,炎症细胞因子水平明显升高有关。而HUC-MSC-exo可通过部分恢复miR-26a-5p/PTEN通路,显著减轻铅对SH-SY5Y细胞的细胞毒性、凋亡和炎症作用。在此,我们得出结论,HUC-MSC-exo可以通过miR-26a-5p/PTEN途径部分减轻铅诱导的SH-SY5Y细胞的毒性作用。
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The toxicity of lead on human neuroblastoma cells was alleviated by HUC-MSC-derived exosomes through miR-26a-5p/PTEN pathway
Lead is a ubiquitous environmental chemical with various toxic damage to human body. This investigation aimed to explore the intervention effect of human umbilical cord mesenchymal stem cells derived exosomes (HUC-MSC-exo) on the neurotoxicity of lead and the relevant mechanism. Differential gradient ultracentrifugation was adopted to isolate HUC-MSC-exo. Nanoparticle tracking assay (NTA), Transmission electron microscope (TEM) technology and exosomal specific biomarkers CD9, CD63 and CD81 were adopted for exosomal characterization. Human neuroblastoma cell (SH-SY5Y) was used as the recipient cell. Confocal laser scanning microscope analysis was conducted to confirm the intake of HUC-MSC-exo by SH-SY5Y cells. Cell migration ability, apoptosis, IL-6, IL-1β and TNF-α were analyzed. The role of miR-26a-5p/PTEN axis was assessed. The result showed that the exposure of SH-SY5Y cells to lead activated the miR-26a-5p/PTEN pathway by down-regulating miR-26a-5p and up-regulating PTEN expression, which was related to the significantly decreased cell migration and increased apoptosis, as well as significantly enhanced levels of inflammatory cytokine as compared with the control. While HUC-MSC-exo could significantly alleviate the cytotoxicity, apoptosis and inflammatory effects induced by lead on SH-SY5Y cells via partially restoring miR-26a-5p/PTEN pathway. Herein, we conclude that HUC-MSC-exo can alleviate lead-induced toxic effects on SH-SY5Y cells partially through miR-26a-5p/PTEN pathway.
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来源期刊
Food and Chemical Toxicology
Food and Chemical Toxicology 工程技术-毒理学
CiteScore
10.90
自引率
4.70%
发文量
651
审稿时长
31 days
期刊介绍: Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.
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