Extracellular vesicles derived from hypoxic human mesenchymal stem cells attenuate GSK3β expression via miRNA-26a in an ischemia-reperfusion injury model

Hyewon Park, Hyelim Park, Dasom Mun, Jiyoung Kang, Hyoeun Kim, Michael Kim, Shanyu Cui, Seung Hyun Lee, Boyoung Joung

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)736-745
Number of pages10
JournalYonsei medical journal
Volume59
Issue number6
DOIs
Publication statusPublished - 2018 Aug

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this