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- W2081248371 abstract "<h3>Objectives</h3> We aimed to investigate whether over-expression of miR-210, an oxide-related miR, could protect mesenchymal stromal cells (MSCs) against apoptosis induced by oxidative stress, and if so, what the potential mechanisms involved. <h3>Methods</h3> MSCs, derived from male SD rats, with forced expression of miR-210 or miR-null by lentivirus infection was incubated with or without Peroxide hydrogen (H<sub>2</sub>O<sub>2</sub>). The reactive oxygen species (ROS) accumulation in MSCs was detected by immunofluoresence probes; cellular survival was measured by MTT assay, Hochest staining and TUNEL examination; superoxidedismutase (SOD) activity and adecreaseinmalonaldehyde (MDA) content were analysed by ELISA assay; and the activation of c-Met pathway was quantified by immunoblot. After application of Crizotinib, an inhibitor specific to c-Met pathway, the above detections were investigated to clarify the mechanisms involved. In an <i>in vivo</i> experiment, the expression of sry gene was checked by quantitative PCR to compare the survival of MSCs-miR-210 and MSCs-miR-null in the infarcted myocardium of female rats on day 4 after transplantation; afterwards, echocardiology was applied to assess the cardiac remodelling and myocardial function in a 4-week follow-up. <h3>Results</h3> It was revealed that forced expression of miR-210 significantly decreased the apoptosis of MSCs against H<sub>2</sub>O<sub>2 </sub>compared with that of miR-null, indicated as follows: a notable decreases in ROS generation (2.34 ± 0.62 vs. 3.98 ± 0.57, <i>P</i><0.05) and apoptotic indices [(15.3 ± 3.87)% vs. (33.8 ± 2.67)%, <i>P</i><0.05]; a dramatic increase in cell viability (2.98 ± 0.67 vs. 1.00 ± 0.74, <i>P</i><0.05), SOD activity (3.91 ± 0.28 vs. 1.00 ± 0.38, <i>P</i><0.05) and MDA content (2.95 ± 0.41 vs. 1.00 ± 0.36, <i>P</i><0.05), which was companied by a remarkable activation of c-Met pathway (2.87 ± 0.34 vs. 1.00 ± 0.52, <i>P</i><0.05). Most importantly, each of the above beneficial effects was attenuated by Crizotinib (<i>P</i> all <0.05). Furthermore, transplantation of MSCs-miR-210 resulted in higher cell survival rates (2.86 ± 0.33 vs. 1.00 ± 0.37, <i>P</i><0.05), therefore significantly improved cardiac remodelling [LVIDd: (5.38 ± 0.61) mm vs. (6.39 ± 0.67) mm, <i>P</i><0.05; LVIDs: (4.92 ± 0.52) mm vs. (5.89 ± 0.51) mm, <i>P</i><0.05;] and statistically ameliorated myocardial function [LVEF: (62.3 ± 5.32)% vs. (42.6 ± 4.38)%, <i>P</i><0.05] than that of MSCs-miR-null. <h3>Conclusions</h3> MiR-210 over-expression may improve MSCs survival in an oxidative stress circumstances through anti-oxidation and c-Met pathways activation, thus enhances their therapeutic effect on myocardial infarction, suggesting that miR-210 was a potential intervention target in the cell-based treatment." @default.
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- W2081248371 date "2013-08-01" @default.
- W2081248371 modified "2023-09-27" @default.
- W2081248371 title "GW24-e3739 MiR-210 Over-expression Enhances Mesenchymal Stromal Cells Survival in an Oxidative Stress Circumstance though Anti-oxidation and c-Met Pathways Activation" @default.
- W2081248371 doi "https://doi.org/10.1136/heartjnl-2013-304613.297" @default.
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