Atorvastatin induces autophagy of mesenchymal stem cells under hypoxia and serum deprivation conditions by activating the mitogenactivated protein kinase/extracellular signal‐regulated kinase pathway
Atorvastatin induces autophagy of mesenchymal stem cells under hypoxia and serum deprivation conditions by activating the mitogenactivated protein kinase/extracellular signal‐regulated kinase pathway
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DOI：
10.3760/cma.j.issn.0366-6999.20132638
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发表时间：
2014-03
影响因子：
6.1
通讯作者：
Na Li;Qian Zhang;H. Qian;Chen Jin;Yuejin Yang;R. Gao
中科院分区：
文献类型：
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作者：
Na Li;Qian Zhang;H. Qian;Chen Jin;Yuejin Yang;R. Gao
Background The survival ratio of implanted mesenchymal stem cells (MSCs) in the infarcted myocardium is low. Autophagy is a complex “self‐eating” process and can be utilized for cell survival. We have found that atorvastatin (ATV) can effectively activate autophagy to enhance MSCs survival during hypoxia and serum deprivation (H/SD). The mitogenactivated protein kinase/extracellular signal‐regulated kinase (MEK/ERK) pathway is a non‐canonical autophagy pathway. We hypothesized that the MEK/ERK pathway mediated ATV‐induced autophagy of MSCs under H/SD. Methods MSCs were pretreated with ATV (0.01–10 mol/L) under H/SD for three hours. For inhibitor studies, the cells were pre‐incubated with the MEK1/2 inhibitor U0126. Cell autophagy was assessed by acidic vesicular organelles (AVO)‐positive cells using flow cytometry, autophagy related protein using Western blotting and autophagosome using transmission electron microscopy. Results Autophagy was elevated in the H/SD group compared with the normal group. ATV further enhanced the autophagic activity as well as the phosphorylation of ERK1/2 evidenced by more AVO‐positive cells ((8.63±0.63)% vs. (5.77±0.44)%, P <0.05), higher LC3‐II/LC3‐I ratio (4.36±0.31 vs. 2.52±0.18, P <0.05) and more autophagosomes. And treatment with U0126 downregulated the phosphorylation of ERK1/2 and attenuated ATV‐induced autophagy. Conclusion The MEK/ERK pathway participates in ATV‐induced autophagy in MSCs under H/SD, and modulation of the pathway could be a novel strategy to improve MSCs survival.
