Extracellular Vesicles Derived from Hypoxic Human Mesenchymal Stem Cells Attenuate GSK3β Expression via miRNA-26a in an Ischemia-Reperfusion Injury Model
Yonsei Medical Journal
;
: 736-745, 2018.
Article
in English
| WPRIM
| ID: wpr-716430
ABSTRACT
PURPOSE:
Bioactive molecules critical to intracellular signaling are contained in extracellular vesicles (EVs) and have cardioprotective effects in ischemia/reperfusion (IR) injured hearts. This study investigated the mechanism of the cardioprotective effects of EVs derived from hypoxia-preconditioned human mesenchymal stem cells (MSCs). MATERIALS ANDMETHODS:
EV solutions (0.4 µg/µL) derived from normoxia-preconditioned MSCs (EVNM) and hypoxia-preconditioned MSCs (EVHM) were delivered in a rat IR injury model. Successful EV delivery was confirmed by the detection of PKH26 staining in hearts from EV-treated rats.RESULTS:
EVHM significantly reduced infarct size (24±2% vs. 8±1%, p < 0.001), and diminished arrhythmias by recovering electrical conduction, INa current, and Cx43 expression. EVHM also reversed reductions in Wnt1 and β-catenin levels and increases in GSK3β induced after IR injury. miRNA-26a was significantly increased in EVHM, compared with EVNM, in real-time PCR. Finally, in in vitro experiments, hypoxia-induced increases in GSK3β expression were significantly reduced by the overexpression of miRNA-26a.CONCLUSION:
EVHM reduced IR injury by suppressing GSK3β expression via miRNA-26a and increased Cx43 expression. These findings suggest that the beneficial effect of EVHM is related with Wnt signaling pathway.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Arrhythmias, Cardiac
/
In Vitro Techniques
/
Reperfusion Injury
/
Connexin 43
/
Mesenchymal Stem Cells
/
Real-Time Polymerase Chain Reaction
/
Wnt Signaling Pathway
/
Extracellular Vesicles
/
Heart
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Yonsei Medical Journal
Year:
2018
Type:
Article
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