Suppression of miR-181a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression |
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Authors: | Seahyoung Lee Ina Yun Onju Ham Se-Yeon Lee Chang Yeon Lee Jun-Hee Park Jiyun Lee Hyang-Hee Seo Eunhyun Choi Ki-Chul Hwang |
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Affiliation: | .Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-do 210-701 Republic of Korea ;.Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, 120-752 Republic of Korea ;.Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, 120-752 Republic of Korea |
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Abstract: | BackgroundLow survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated.ResultsH2O2 (600 μM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2.ConclusionsThese findings suggest that H2O2-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues. |
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Keywords: | Hexokinase II miRNA-181a Cell death Mesenchymal stem cell |
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