miR-100a-5p-enriched exosomes derived from mesenchymal stem cells enhance the anti-oxidant effect in a Parkinson's disease model via regulation of Nox4/ROS/Nrf2 signaling.

Autor: He S; Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.; Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, 510515, Guangdong, China.; Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, 510515, Guangdong, China., Wang Q; Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.; Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, 510515, Guangdong, China.; Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, 510515, Guangdong, China., Chen L; ImStem Biotechnology, Inc., 400 Farmington Avenue R1808, Farmington, CT, 06030, USA.; Zhuhai Hengqin ImStem Biotechnology Co., Ltd, Hengqin New District Huandao Donglu 1889 Building 3, Zhuhai, 519000, Guangdong, China., He YJ; ImStem Biotechnology, Inc., 400 Farmington Avenue R1808, Farmington, CT, 06030, USA.; Zhuhai Hengqin ImStem Biotechnology Co., Ltd, Hengqin New District Huandao Donglu 1889 Building 3, Zhuhai, 519000, Guangdong, China., Wang X; ImStem Biotechnology, Inc., 400 Farmington Avenue R1808, Farmington, CT, 06030, USA.; Zhuhai Hengqin ImStem Biotechnology Co., Ltd, Hengqin New District Huandao Donglu 1889 Building 3, Zhuhai, 519000, Guangdong, China., Qu S; Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. sgq9528@smu.edu.cn.; Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, 510515, Guangdong, China. sgq9528@smu.edu.cn.; Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, 510515, Guangdong, China. sgq9528@smu.edu.cn.; Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, 341000, Jiangxi, China. sgq9528@smu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2023 Oct 24; Vol. 21 (1), pp. 747. Date of Electronic Publication: 2023 Oct 24.
DOI: 10.1186/s12967-023-04638-x
Abstrakt: Background: The pathogenesis of Parkinson's disease (PD) has not been fully elucidated, and there are no effective disease-modifying drugs for the treatment of PD. Mesenchymal stem cells have been used to treat several diseases, but are not readily available.
Methods: Here, we used phenotypically uniform trophoblast stage-derived mesenchymal stem cells (T-MSCs) from embryonic stem cells, which are capable of stable production, and their exosomes (T-MSCs-Exo) to explore the molecular mechanisms involved in dopaminergic (DA) neuron protection in PD models using experimental assays (e.g., western blotting, immunofluorescence and immunohistochemistry staining).
Results: We assessed the levels of DA neuron injury and oxidative stress in MPTP-induced PD mice and MPP + -induced MN9D cells after treating them with T-MSCs or T-MSCs-Exo. Furthermore, T-MSCs-Exo miRNA sequencing analysis revealed that miR-100-5p-enriched T-MSCs-Exo directly targeted the 3' UTR of NOX4, which could protect against the loss of DA neurons, maintain nigro-striatal system function, ameliorate motor deficits, and reduce oxidative stress via the Nox4-ROS-Nrf2 axis in PD models.
Conclusions: The study suggests that miR-100-5p-enriched T-MSCs-Exo may be a promising biological agent for the treatment of PD. Schematic summary of the mechanism underlying the neuroprotective actions of T-MSCs-Exo in PD. T-MSCs Exo may inhibit the expression level of the target gene NOX4 by delivering miR-100-5p, thereby reducing ROS production and alleviating oxidative stress via the Nox4-ROS-Nrf2 axis, thus improving DA neuron damage in PD.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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