Author:
Zhang You,Lei Wei,Yan Weiya,Li Xizhe,Wang Xiaolin,Zhao Zhenao,Hui Jie,Shen Zhenya,Yang Junjie
Abstract
Abstract
Background
Overexpression of Pim-1 in stem/progenitor cells stimulated cell cycling and enhanced cardiac regeneration in vivo. We proposed that hypoxic preconditioning could increase survival of bone marrow mesenchymal stem cells (MSCs) via upregulation of Pim-1 and aimed to determine the microRNAs that modulate the expression of Pim-1.
Methods and results
MSCs were subjected to hypoxia exposure. The expression of Pim-1 in MSCs was enhanced in a time-dependent manner, detected by quantitative PCR and western blot. miR-206 is predicted as one of the potential microRNAs that target Pim-1. The expression of miR-206 was decreased in hypoxic MSCs and reversely correlated with Pim-1 expression. Luciferase activity assay further confirmed Pim-1 as a putative target of miR-206. In addition, gain and loss-of-function studies with miR-206 mimics and inhibitors showed that inhibition of miR-206 in hypoxic MSCs promoted the migration ability of the cells, prevented cell apoptosis, and protected membrane potential of mitochondria, while the benefits were all blocked by Pim-1 inhibitor. In an acute model of myocardial infarction, transplanted hypoxic MSCs showed a significantly improved survival as compared with hypoxic MSCs overexpressing miR-206.
Conclusions
Hypoxic preconditioning could increase short-term survival of bone marrow MSCs via upregulation of Pim-1, and miR-206 was one of the critical regulators in this process.
Funder
National Natural Science Foundation of China
Suzhou Municipal Science and Technology Project of China
Natural Science Foundation of Jiangsu Province
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Medicine,Medicine (miscellaneous)
Cited by
34 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献