Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, 1838 Guangzhou Road North, Guangzhou 510515, PR China; Public Health Service Centre of Baoan District, Shenzhen City 518000, PR China.
Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, 1838 Guangzhou Road North, Guangzhou 510515, PR China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117120. doi: 10.1016/j.ecoenv.2024.117120. Epub 2024 Oct 1.
Mesenchymal stem cell - originated exosomes (MSC-exo) are promising non-cellular treatment agents for various diseases. The present study aimed to explore whether human umbilical cord MSC - originated exosomes (HUC-MSC-exo) have the function of protecting human cells (16HBE) against the damage caused by HQ and the related mechanism. HUC-MSC-exo was isolated with differential gradient ultracentrifugation method and characterized by using transmission electron microscope (TEM). 16HBE cells were used as the tool cells and co-cultured with HUC-MSC-exo. Confocal laser scanning microscope was employed to confirm the ingestion of HUC-MSC-exo by 16HBE. Cell proliferation, migration, oxidative stress, DNA and chromosome damages of 16HBE were analyzed under HQ stress, and the role of miR-221/PTEN axis was investigated. Our data showed that under HQ stress, different groups of cells exhibited significantly decreased proliferation and migration abilities, and significant oxidative stress, DNA and chromosome damage effects. HUC-MSC-exo could alleviate the cytotoxic, oxidative stress and genotoxic damage effects of HQ on 16HBE cells. Mechanistically, HQ exposure up-regulated the level of miR-221 and down-regulated PTEN, while HUC-MSC-exo could significantly reduce the level of miR-221 and promote PTEN expression, which was involved in alleviating the toxic effects of HQ on 16HBE cells. Our data indicates that HUC-MSC-exo can alleviate the oxidative stress, cytotoxic and genotoxic effects of HQ on 16HBE cells via miR-221/PTEN pathway, and it may be a promising agent for protecting against the toxicity of HQ.
间充质干细胞来源的外泌体（MSC-exo）是一种很有前途的非细胞治疗药物，可用于治疗多种疾病。本研究旨在探讨人脐带间充质干细胞来源的外泌体（HUC-MSC-exo）是否具有保护人细胞（16HBE）免受 HQ 损伤的作用及其相关机制。采用差速梯度超速离心法分离 HUC-MSC-exo，并用透射电子显微镜（TEM）进行鉴定。以 16HBE 细胞为工具细胞，与 HUC-MSC-exo 共培养。应用共聚焦激光扫描显微镜确认 16HBE 摄取 HUC-MSC-exo。在 HQ 应激下分析 16HBE 的细胞增殖、迁移、氧化应激、DNA 和染色体损伤，探讨 miR-221/PTEN 轴的作用。结果显示，在 HQ 应激下，不同组细胞的增殖和迁移能力明显下降，氧化应激、DNA 和染色体损伤明显。HUC-MSC-exo 可减轻 HQ 对 16HBE 细胞的细胞毒性、氧化应激和遗传毒性损伤作用。机制上，HQ 暴露上调 miR-221 水平，下调 PTEN，而 HUC-MSC-exo 可显著降低 miR-221 水平，促进 PTEN 表达，从而减轻 HQ 对 16HBE 细胞的毒性作用。本研究表明，HUC-MSC-exo 可通过 miR-221/PTEN 通路减轻 HQ 对 16HBE 细胞的氧化应激、细胞毒性和遗传毒性作用，可能是一种有前途的 HQ 毒性保护剂。
