- Academic Editor
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†These authors contributed equally.
Background: Experimental investigations have reported
the efficacy of marrow mesenchymal stem cell-derived exosomes (MSC-Exos) for the
treatment of ischemic stroke. The therapeutic mechanism, however, is still
unknown. The purpose of the study is to show whether MSC-Exos increases
astrocytic glutamate transporter-1 (GLT-1) expression in response to ischemic
stroke and to investigate further mechanisms. Methods and Results:
An in vitro ischemia model (oxygen-glucose deprivation/reperfusion,
OGD/R) was used. MSC-Exos was identified by Western blot (WB) and transmission
electron microscopy (TEM). To further investigate the mechanism, MSC-Exos,
miR-124 inhibitor, and mimics, and a mTOR pathway inhibitor (rapamycin, Rap) were
used. The interaction between GLT-1 and miR-124 was analyzed by luciferase
reporter assay. The GLT-1 RNA expression and miR-124 was assessed by quantitative real-time polymerase chain reaction (qRTPCR). The
protein expressions of GLT-1, S6, and pS6 were detected by WB. Results
demonstrated that MSC-Exos successfully inhibited the decrease of GLT-1 and
miR-124 expression and the increase of pS6 expression in
astrocytes after OGD/R. miR-124 inhibitor suppressed the effect of MSC-Exos on
GLT-1 upregulation after OGD/R. Rapamycin notably decreased pS6 expression with
significantly higher GLT-1 expression in astrocytes injured by OGD/R. Luciferase
activity of the reporter harboring the wild-type or mutant GLT-1 3