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Biol. Res ; 48: 1-7, 2015. graf
Article Dans Anglais | LILACS | ID: biblio-950809

Résumé

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 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. RESULTS: H2O2 (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. CONCLUSIONS: These 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.


Sujets)
Humains , Apoptose , microARN/métabolisme , Cellules souches mésenchymateuses/anatomopathologie , Gliome/anatomopathologie , Hexokinase/métabolisme , Peroxyde d'hydrogène/toxicité , Glycoprotéines membranaires/génétique , Glycoprotéines membranaires/métabolisme , Différenciation cellulaire , Mouvement cellulaire , Survie cellulaire , Espèces réactives de l'oxygène , Sémaphorines/génétique , Sémaphorines/métabolisme , microARN/antagonistes et inhibiteurs , Cellules souches mésenchymateuses/effets des médicaments et des substances chimiques , Cellules souches mésenchymateuses/enzymologie , Réaction de polymérisation en chaine en temps réel , Gliome/métabolisme , Peroxyde d'hydrogène/administration et posologie , Mitochondries/enzymologie , Invasion tumorale
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