1. Human umbilical cord mesenchymal stem cells mitigate A1 astrocyte neuroinflammation induced by 1,2-dichloroethane via ERBB pathway inhibition
- Author
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Jiaxin Du, Yizhou Zhong, Bingchi Fan, Xiaohong Yang, Rongyi Ye, Yuji Huang, Zhiming Li, Boxuan Liang, Hongyi Xian, Yanhong Deng, Xiyun Huang, Xiaoqing Chen, Congying Shi, Xibao Yu, Banghua Wu, Xingfen Yang, and Zhenlie Huang
- Subjects
1,2-Dichloroethane ,Exosome ,miRNAs ,HUCMSCs ,REPS2 ,Astrocyte activation ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
1,2-Dichloroethane (1,2-DCE), a prevalent industrial and environmental contaminant, induces toxic encephalopathy through inhalation, leading to neurotoxic effects and inflammation-driven brain edema. Human umbilical cord mesenchymal stem cells (HUCMSCs) secrete bioactive factors, including miRNAs, proteins, and lipids via exosomes, exhibiting anti-inflammatory and immune-regulatory properties. However, their potential in treating 1,2-DCE-induced neuroinflammation and the underlying mechanisms remain unclear. This study investigates how HUCMSCs mitigate 1,2-DCE-induced neuroinflammation. We exposed SVG p12 cells to 1,2-DCE and assessed inflammatory markers and A1 astrocyte activation. Co-culturing these cells with HUCMSCs, we used RNA sequencing to analyze inflammatory modulation. Additionally, HUCMSCs were administered to CD-1 male mice post-1,2-DCE exposure, evaluating the reduction in A1 astrocyte inflammation via behavioral tests, molecular analyses, and tissue staining. Pre-treating HUCMSCs with exosome inhibitors and co-culturing them with 1,2-DCE-treated SVG p12 cells investigated miRNA transfer. Results showed that 1,2-DCE activated A1 astrocytes, leading to increases in interleukin-1β (IL-1β, 4.9-fold), tumor necrosis factor-α (TNF-α, 2.5-fold), complement 3 (C3, 2.1-fold), and glial fibrillary acidic protein (GFAP, 1.4-fold). HUCMSCs effectively reversed 1,2-DCE-induced A1 astrocyte inflammation, attenuating IL-1β, TNF-α, and A1 astrocyte activation. RNA-seq highlighted modulation of the erb-b2 receptor tyrosine kinase (ERBB) pathway via Ral-binding protein 1-associated Eps domain-containing 2 (REPS2). In vivo confirmation underscored these findings. Importantly, HUCMSC-derived exosomes, particularly miR-3064–5p, reversed 1,2-DCE-activated A1 astrocyte inflammation, suggesting therapeutic potential. Collectively, HUCMSCs alleviate 1,2-DCE-induced neuroinflammation via exosome-mediated miR-3064–5p secretion, targeting REPS2 to mitigate neuroinflammation. This study advances the understanding of their therapeutic roles and highlights HUCMSC exosomal miRNA transfer for treating 1,2-DCE-induced neuroinflammatory conditions.
- Published
- 2024
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