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

7 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

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Reperfusion Injury
MicroRNAs
Mesenchymal Stromal Cells
Connexin 43
Cell Hypoxia
Catenins
Wnt Signaling Pathway
Extracellular Vesicles
Hypoxia
Reperfusion
Cardiac Arrhythmias
Real-Time Polymerase Chain Reaction
Ischemia
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Park, Hyewon ; Park, Hyelim ; Mun, Dasom ; Kang, Jiyoung ; Kim, Hyoeun ; Kim, Michael ; Cui, Shanyu ; Lee, Seung Hyun ; Joung, Boyoung. / Extracellular vesicles derived from hypoxic human mesenchymal stem cells attenuate GSK3β expression via miRNA-26a in an ischemia-reperfusion injury model. In: Yonsei medical journal. 2018 ; Vol. 59, No. 6. pp. 736-745.
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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.",
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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. / Park, Hyewon; Park, Hyelim; Mun, Dasom; Kang, Jiyoung; Kim, Hyoeun; Kim, Michael; Cui, Shanyu; Lee, Seung Hyun; Joung, Boyoung.

In: Yonsei medical journal, Vol. 59, No. 6, 08.2018, p. 736-745.

Research output: Contribution to journalArticle

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AU - Park, Hyewon

AU - Park, Hyelim

AU - Mun, Dasom

AU - Kang, Jiyoung

AU - Kim, Hyoeun

AU - Kim, Michael

AU - Cui, Shanyu

AU - Lee, Seung Hyun

AU - Joung, Boyoung

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N2 - 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.

AB - 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.

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