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Mesenchymal Stem Cell–Derived Extracellular Vesicles Alleviate M1 Microglial Activation in Brain Injury of Mice With Subarachnoid Hemorrhage via microRNA-140-5p Delivery.

Authors :
Qian, Yu
Li, Qiaoyu
Chen, Lulu
Sun, Jinyu
Cao, Kan
Mei, Zhaojun
Lu, Xinyu
Source :
International Journal of Neuropsychopharmacology; Apr2022, Vol. 25 Issue 4, p328-338, 11p
Publication Year :
2022

Abstract

Background It is documented that mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs) to modulate subarachnoid hemorrhage (SAH) development. miR-140-5p expression has been detected in MSC-derived EVs, while the mechanism of MSC-derived EVs containing miR-140-5p in SAH remains unknown. We aim to fill this void by establishing SAH mouse models and extracting MSCs and MSC-EVs. Methods After ALK5 was silenced in SAH mice, neurological function was evaluated, neuron apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling with NeuN staining, and expression of serum inflammatory factors (interleukin-6, interleukin-1β, and tumor necrosis factor-α) was determined by enzyme-linked immunosorbent assay. The effect of ALK5 on NOX2 expression was assessed by western-blot analysis. Targeting the relationship between miR-140-5p and ALK5 was evaluated by dual luciferase assay. Following extraction of MSCs and MSC-EVs, EVs and miR-140-5p were labeled by PKH67 and Cy3, respectively, to identify the transferring of miR-140-5p by MSC-EVs. SAH mice were treated with EVs from miR-140-5p mimic/inhibitor-transfected MSCs to detect effects of MSC-EV-miR-140-5p on brain injury and microglial polarization. Results ALK5 silencing increased the neurological score and reduced neuron apoptosis and neuroinflammation in SAH mice. ALK5 silencing inhibited M1 microglia activation by inactivating NOX2. ALK5 was a target gene of miR-140-5p. MSC-derived EVs contained miR-140-5p and transferred miR-140-5p into microglia. MSC-EV-delivered miR-140-3p reduced ALK5 expression to contribute to repression of brain injury and M1 microglia activation in SAH mice. Conclusions MSC-derived EVs transferred miR-140-5p into microglia to downregulate ALK5 and NOX2, thus inhibiting M1 microglia activation in SAH mice. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14611457
Volume :
25
Issue :
4
Database :
Complementary Index
Journal :
International Journal of Neuropsychopharmacology
Publication Type :
Academic Journal
Accession number :
156498069
Full Text :
https://doi.org/10.1093/ijnp/pyab096