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.
Highlights
Low survival rate of transplanted cells compromises the efficacy of cell therapy
HK family is composed of four different isotypes (1 to 4, or I to IV) and they can initiate the glycolysis pathway where glucose is converted to glucose-6-phosphate [6]
We examined the possibility of miRNA-dependent Hexokinase II (HKII) regulation during ROS-induced death of mesenchymal stem cells (MSCs)
Summary
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 expression of HKII in MSCs exposed to H2O2 was evaluated, and HKIItargeting 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. High death rate of the transplanted cells has hampered the efficacy of stem cell-based cell therapy [3]. One of the major reasons for such low survival of transplanted cells is that the transplanted cells are immediately exposed to a harsh microenvironment (i.e., low tissue oxygen and nutrients, and increased reactive oxygen species (ROS) in case of ischemic heart disease), which can induce various types of cell death, including apoptosis [4]. A previous study reported that myocardial ischemia/reperfusion (I/R) injury decreased the cardiac expression of HKII as well
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
