We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
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; Kim, Michael; Shanyu Cui; Seung-Hyun Lee; Boyoung Joung
- 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.
- Subjects
MESENCHYMAL stem cells; GLYCOGEN synthase kinase-3; MICRORNA; REPERFUSION injury; GENE expression
- Publication
Yonsei Medical Journal, 2018, Vol 59, Issue 6, p736
- ISSN
0513-5796
- Publication type
Article
- DOI
10.3349/ymj.2018.59.6.736