The toxicity of lead on human neuroblastoma cells was alleviated by HUC-MSC-derived exosomes through miR-26a-5p/PTEN pathway

• Published in: Food and chemical toxicology 2024-12, Vol.196, p.115177, Article 115177
• Main Authors: Xiong, Yiren, He, Jiayi, He, Shanshan, Hu, Zuqing, Ouyang, Di, Liu, Renyi, Gao, Zhenjie, Zhang, Weiguang, Kang, Zhujun, Lan, Shuyi, Wang, Yang, Diallo, Fatoumata, Hu, Dalin
• Format: Article
• Language: English
• Subjects: Exosomes; HUC-MSC; Intervention; Lead; Neurotoxicity
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2024.115177

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. •The miR-26a-5p/PTEN axis of SH-SY5Y cells was activated by lead.•Lead induced significant toxic effects on SH-SY5Y cells.•HUC-MSC-exo could be ingested by SH-SY5Y cells.•The toxicity of lead on SH-SY5Y cells was alleviated by HUC-MSC-exo via miR-26a-5p/PTEN.