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Suppression of miR-181a attenuates H(2)O(2)-induced death of mesenchymal stem cells by maintaining hexokinase II expression

BACKGROUND: Low 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...

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Detalles Bibliográficos
Autores principales: Lee, Seahyoung, Yun, Ina, Ham, Onju, Lee, Se-Yeon, Lee, Chang Yeon, Park, Jun-Hee, Lee, Jiyun, Seo, Hyang-Hee, Choi, Eunhyun, Hwang, Ki-Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539679/
https://www.ncbi.nlm.nih.gov/pubmed/26283227
http://dx.doi.org/10.1186/s40659-015-0036-5
Descripción
Sumario:BACKGROUND: Low 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 H(2)O(2). The expression of HKII in MSCs exposed to H(2)O(2) was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H(2)O(2) 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 H(2)O(2)-induced apoptosis of MSC was evaluated. RESULTS: H(2)O(2) (600 μM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H(2)O(2) increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H(2)O(2)-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H(2)O(2). CONCLUSIONS: These findings suggest that H(2)O(2)-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.