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Bone marrow mesenchymal stem cell-derived exosomes carrying long noncoding RNA ZFAS1 alleviate oxidative stress and inflammation in ischemic stroke by inhibiting microRNA-15a-5p

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Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Background/aim

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes can prevent oxidative stress and inflammation in cerebral ischemia-reperfusion injury. This study intended to assess influences of BMSC-released exosomes on oxidative stress and inflammation following ischemic stroke.

Methods

In vitro and in vivo models were developed using oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO), respectively. After exosome isolation, co-culture experiments of BMSCs or BMSC-derived exosomes and OGD/R-treated BV-2 cells were implemented to evaluate the impacts of BMSCs or BMSC-secreted exosomes on proliferation, inflammation, oxidative stress, and apoptosis. The gain-of-function experiments of ZFAS1 or microRNA (miR)-15a-5p were conducted to investigate the associated mechanisms. Besides, MCAO mice were injected with exosomes from BMSCs overexpressing ZFAS1 for in vivo verification. The binding of ZFAS1 to miR-15a-5p was assessed through dual-luciferase reporter gene assay.

Results

Co-culture with BMSCs accelerated proliferation and downregulated IL-1β, IL-6, and TNF-α in OGD/R-exposed BV-2 cells, accompanied by increased SOD level and decreased MDA level and apoptosis, all of which were nullified by inhibiting exosome secretion. Mechanistically, ZFAS1 bound to miR-15a-5p to negatively orchestrate its expression. In addition, BMSC-released exosomes or BMSC-secreted exosomal ZFAS1 augmented proliferation but reduced oxidative stress, apoptosis, and inflammation in OGD/R-exposed BV-2 cells, whereas these impacts of BMSC-released exosomal ZFAS1 were nullified by overexpressing miR-15a-5p. Moreover, BMSC-derived exosomal ZFAS1 diminished MCAO-induced oxidative stress, cerebral infarction, and inflammation in mice.

Conclusions

Conclusively, BMSC-released exosomes might carry long noncoding RNA ZFAS1 to curb oxidative stress and inflammation related to ischemic stroke, which was possibly realized through miR-15a-5p inhibition.

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Authors and Affiliations

  1. Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169, Donghu Road, Wuchang District, 430071, Wuhan, Hubei, P.R. China

    Huaitao Yang & Jincao Chen

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  1. Huaitao Yang
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  2. Jincao Chen
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Contributions

JCC conceived the ideas. JCC designed the experiments. HTY analyzed the data. JCC provided critical materials. JCC and HTY wrote the manuscript. JCC supervised the study. All the authors have read and approved the final version for publication.

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Correspondence to Jincao Chen.

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Yang, H., Chen, J. Bone marrow mesenchymal stem cell-derived exosomes carrying long noncoding RNA ZFAS1 alleviate oxidative stress and inflammation in ischemic stroke by inhibiting microRNA-15a-5p. Metab Brain Dis 37, 2545–2557 (2022). https://doi.org/10.1007/s11011-022-00997-4

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  • DOI: https://doi.org/10.1007/s11011-022-00997-4

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