Dataset Information

Extracellular Vesicles Derived from Hypoxic Human Mesenchymal Stem Cells Attenuate GSK3? Expression via miRNA-26a in an Ischemia-Reperfusion Injury Model.

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 ?g/?L) derived from normoxia-preconditioned MSCs (EV(NM)) and hypoxia-preconditioned MSCs (EV(HM)) 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

EV(HM) significantly reduced infarct size (24±2% vs. 8±1%, p<0.001), and diminished arrhythmias by recovering electrical conduction, I(Na) current, and Cx43 expression. EV(HM) also reversed reductions in Wnt1 and ?-catenin levels and increases in GSK3? induced after IR injury. miRNA-26a was significantly increased in EV(HM), compared with EV(NM), in real-time PCR. Finally, in in vitro experiments, hypoxia-induced increases in GSK3? expression were significantly reduced by the overexpression of miRNA-26a.

Conclusion

EV(HM) reduced IR injury by suppressing GSK3? expression via miRNA-26a and increased Cx43 expression. These findings suggest that the beneficial effect of EVHM is related with Wnt signaling pathway.

SUBMITTER: Park H

PROVIDER: S-EPMC6037597 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Extracellular Vesicles Derived from Hypoxic Human Mesenchymal Stem Cells Attenuate GSK3β Expression via miRNA-26a in an Ischemia-Reperfusion Injury Model.

Park Hyewon H Park Hyelim H Mun Dasom D Kang Jiyoung J Kim Hyoeun H Kim Michael M Cui Shanyu S Lee Seung Hyun SH Joung Boyoung B

Yonsei medical journal 20180801 6

<h4>Purpose</h4>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).<h4>Materials and methods</h4>EV solutions (0.4 μg/μL) derived from normoxia-preconditioned MSCs (EV(NM)) and hypoxia-preconditioned MSCs (EV(HM)) were de ...[more]

PMID: 29978610

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