microRNA-206 is involved in survival of hypoxia preconditioned mesenchymal stem cells through targeting Pim-1 kinase.
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.


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.
Department of Cardiology of the First Affiliated Hospital, Soochow University, Suzhou, China.
You
Y
Zhang
Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University, Suzhou, China.
Wei
W
Lei
Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University, Suzhou, China.
Weiya
W
Yan
Department of Cardiovascular Surgery, Affiliated Shanghai 1st People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Xizhe
X
Li
Department of Thoracic and Cardiovascular Surgery, Northern Jiangsu People's Hospital, Yangzhou, China.
Xiaolin
X
Wang
Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University, Suzhou, China.
Zhenao
Z
Zhao
Department of Cardiology of the First Affiliated Hospital, Soochow University, Suzhou, China. huijie92@163.com.
Jie
J
Hui
Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University, Suzhou, China. uuzyshen@aliyun.com.
Zhenya
Z
Shen
Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University, Suzhou, China. jjyang@suda.edu.cn.
Junjie
J
Yang
D000818:Animals; D000070416:Antagomirs / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D015687:Cell Hypoxia; D002465:Cell Movement; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D019194:Ischemic Preconditioning; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D000070416:Antagomirs; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; C522220:mirn206 microRNA, rat; D008156:Luciferases; C496637:Pim1 protein, rat; D051573:Proto-Oncogene Proteins c-pim-1
Apoptosis; Hypoxia; Mesenchymal stem cells; Pim-1; miR-206