title: MiRNA-486 regulates angiogenic activity and survival of mesenchymal stem cells under hypoxia through modulating Akt signal.
abstract: MicroRNA-486 (miR-486) was first identified from human fetal liver cDNA library and validated as a regulator of hematopoiesis. Its roles in regulating the biological function of bone marrow-derived mesnechymal stem cells (BM-MSCs) under hypoxia have not been explored yet. In this study, we demonstrated that exposure to hypoxia upregulates miR-486 expression in BM-MSCs. Lentivirus-mediated overexpression of miR-486 resulted in increase of hepatocyte growth factor (HGF) and vascular endothelial growth factor(VEGF) in both mRNA and protein levels. MiR-486 expression also promotes proliferation and reduces apoptosis of BM-MSCs. Whereas MiR-486 knockdown downregulated the secretion of HGF and VEGF and induced apoptosis of BM-MSCs. Furthermore, PTEN-PI3K/AKT signaling was validated to be involved in changes of BM-MSC biological functions regulated by miR-486. These results suggested that MiR-486 mediated the hypoxia-induced angiogenic activity and promoted the proliferation and survival of BM-MSCs through regulating PTEN-PI3K/AKT signaling. These findings might provide a novel understanding of effective therapeutic strategy for hypoxic-ischemic diseases.
authors.affiliation: High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001, PR China; Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Department of Respiration, Qinghai Provincial People's Hospital, Xining, PR China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Shi
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Xiao
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Department of Hematology, Peking University First Hospital, Beijing, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yin
authors.affiliation: High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001, PR China; Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Xu
authors.affiliation: High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001, PR China. Electronic address: geriligao@hotmail.com.
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Ge
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: wangls@bmi.ac.cn.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wang
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D042501:Angiogenic Proteins; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; D051058:Oncogene Protein v-akt; D010100:Oxygen
keywords: Bone marrow mesenchymal stem cells; Hypoxia; PTEN-PI3K/AKT signaling; miR-486