Extracellular Vesicles Derived from Hypoxic Human Mesenchymal Stem Cells Attenuate GSK3β Expression via miRNA-26a in an Ischemia-Reperfusion Injury Model.
10.3349/ymj.2018.59.6.736
- Author:
Hyewon PARK
1
;
Hyelim PARK
;
Dasom MUN
;
Jiyoung KANG
;
Hyoeun KIM
;
Michael KIM
;
Shanyu CUI
;
Seung Hyun LEE
;
Boyoung JOUNG
Author Information
1. Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea. cby6908@yuhs.ac
- Publication Type:Original Article
- Keywords:
Extracellular vesicles;
ischemia reperfusion;
arrhythmia;
GSK3β;
miRNA-26a
- MeSH:
Animals;
Arrhythmias, Cardiac;
Connexin 43;
Extracellular Vesicles*;
Heart;
Humans*;
In Vitro Techniques;
Mesenchymal Stromal Cells*;
Rats;
Real-Time Polymerase Chain Reaction;
Reperfusion Injury*;
Wnt Signaling Pathway
- From:Yonsei Medical Journal
2018;59(6):736-745
- CountryRepublic of Korea
- Language:English
-
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 AND METHODS: 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.
