期刊
MEDICAL SCIENCE MONITOR
卷 24, 期 -, 页码 264-271出版社
INT SCIENTIFIC INFORMATION, INC
DOI: 10.12659/MSM.904618
关键词
Cell Survival; Mesenchymal Stromal Cells; MicroRNAs; Oxidative Stress
资金
- Natural Science Foundation Project of CQ CSCT [2011BB5138]
- National Natural Science Foundation of China [81100475, 81271385]
Background: Mesenchymal stromal/stem cells (MSCs)are broadly used for many diseases, but the efficacy of MSC engraftment is very low due to low viability and high cell death rate under a stressful microenvironment. The present study aimed to investigate whether microRNA-34a (miR-34a), which is a downstream target of P53, is involved in H2O2 -induced MSC cell death. Material/Method: Human bone marrow MSCs (hMSCs) were purchased from Lonza and were cultured as previously described. hMSCs were transfected with miR-34a inhibitor and exposed to H2O2. Cell proliferation assay was used to assess the survival rate of hMSCs. Real-time PCR and Western blot analysis were used to examine proliferation and survival ability of hMSCs. Results: H2O2 exposure significantly increased miR-34a expression in human bone marrow MSCs. H2O2 challenge induced massive MSC cell death along with reduction of expression of proliferation marker Ki67 and survival-related genes Bcl-2 and Survivin. Transfection of miR-34a inhibitor anti-34a led to a significant protective effect and rescued MSC cell death triggered by H2O2 exposure by 50%. Moreover, anti-34a dramatically increased Bcl-2 and Ki67 mRNA expression levels by over 10-fold compared to the mock control group under H2O2 exposure. The protein levels of Bcl-2 and Survivin were also rescued by anti-34a treatment by 50%. Conclusions: Our results suggest that miR-34a plays a key role in oxidative stress-induced MSC cell death, and targeting miR-34a might be a promising strategy to enhance the survival rate of engrafted stem cells, which may improve therapeutic outcome.
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