The Second Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China; Yunnan Provincial Clinical Research Center for Neurological Disease, Kunming 650032, Yunnan, China.
Yunnan Provincial Clinical Research Center for Neurological Disease, Kunming 650032, Yunnan, China; Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.
Neurosci Lett. 2023 Sep 25;814:137437. doi: 10.1016/j.neulet.2023.137437. Epub 2023 Aug 20.
This study aims to elucidate the role of miR-23b-3p in mesenchymal stem cell exosomes in regulating the Wnt signaling pathway to promote autophagy of neurons and alleviate Parkinson's disease (PD) symptoms. We generated rat and cellular PD models with 6-OHDA, treated them with mesenchymal stem cell exosomes rich in miR-23b-3p and determined the expression of α-syn and Wnt/β-catenin pathway and autophagy-related genes. In the plasma of PD patients, the levels of miR-23b-3p and the Wnt/β-catenin pathway-related genes β-catenin and DAT were low, while α-syn expression was high. In the PD cell model, miR-23b-3p was downregulated, the Wnt pathway was inhibited, α-syn was upregulated, neuron autophagy was inhibited, and the revitalization of the Wnt/β-catenin pathway could promote the autophagy of neurons. Coculture of miR-23b-3p-enriched exosomes with MN9D cells confirmed that miR-23b-3p-enriched exosomes could promote autophagy in MN9D cells in a PD cell model. Moreover, animal experiments confirmed the results of the cell experiments. Therefore, miR-23b-3p-enriched mesenchymal stem cell exosomes promote neuronal autophagy by regulating the Wnt signaling pathway, thus alleviating PD progression and providing an important basis for the clinical treatment of PD.
本研究旨在阐明 miR-23b-3p 在间充质干细胞外泌体中调节 Wnt 信号通路以促进神经元自噬并减轻帕金森病 (PD) 症状中的作用。我们使用 6-OHDA 生成大鼠和细胞 PD 模型，用富含 miR-23b-3p 的间充质干细胞外泌体处理它们，并确定α-syn 和 Wnt/β-catenin 途径和自噬相关基因的表达。在 PD 患者的血浆中，miR-23b-3p 的水平和 Wnt/β-catenin 途径相关基因β-catenin 和 DAT 较低，而α-syn 的表达较高。在 PD 细胞模型中，miR-23b-3p 下调，Wnt 途径被抑制，α-syn 上调，神经元自噬受到抑制，而 Wnt/β-catenin 途径的再活化可以促进神经元自噬。将富含 miR-23b-3p 的外泌体与 MN9D 细胞共培养证实，富含 miR-23b-3p 的外泌体可以在 PD 细胞模型中促进 MN9D 细胞的自噬。此外，动物实验证实了细胞实验的结果。因此，富含 miR-23b-3p 的间充质干细胞外泌体通过调节 Wnt 信号通路促进神经元自噬，从而减轻 PD 的进展，为 PD 的临床治疗提供了重要依据。
