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

Authors
 Hyewon Park  ;  Hyelim Park  ;  Dasom Mun  ;  Jiyoung Kang  ;  Hyoeun Kim  ;  Michael Kim  ;  Shanyu Cui  ;  Seung-Hyun Lee  ;  Boyoung Joung 
Citation
 YONSEI MEDICAL JOURNAL, Vol.59(6) : 736-745, 2018 
Journal Title
 YONSEI MEDICAL JOURNAL 
ISSN
 0513-5796 
Issue Date
2018
MeSH
Animals ; Connexin 43 ; Extracellular Vesicles ; Glycogen Synthase Kinase 3 beta/antagonists & inhibitors ; Glycogen Synthase Kinase 3 beta/genetics ; Glycogen Synthase Kinase 3 beta/metabolism* ; Humans ; Hypoxia/metabolism ; Hypoxia/physiopathology* ; Immunohistochemistry ; Ischemia/physiopathology* ; Male ; Mesenchymal Stromal Cells/metabolism ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/genetics ; MicroRNAs/metabolism* ; RNA, Small Interfering/metabolism ; Rats ; Reperfusion Injury* ; beta Catenin
Keywords
Extracellular vesicles ; GSK3β ; arrhythmia ; ischemia reperfusion ; miRNA-26a
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 (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 β-catenin levels and increases in GSK3β 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 GSK3β expression were significantly reduced by the overexpression of miRNA-26a. CONCLUSION: EV(HM) 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.
Files in This Item:
T201802316.pdf Download
DOI
10.3349/ymj.2018.59.6.736
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Seung Hyun(이승현) ORCID logo https://orcid.org/0000-0001-7549-9430
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163164
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