title: The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells.
abstract: Recent developments and re-emergence of interferon α (IFN-α) have renewed interest in the therapy for patients with chronic myeloid leukemia (CML). Related molecular mechanism may be the direct effect of IFN-α on CML stem cells. Human mesenchymal stromal cells (hMSCs) are important to protect CML stem cells, and IFN-α was described as a potential inhibitor of hMSCs. However, the exact mechanism remains obscure. PML as a known tumor suppressor locates downstream of the IFN-α pathway, and little is known about the PML gene regulation in hMSCs. The aim of this study was to investigate the effects of IFN-α on hMSCs and defined the role of PML involved in this process. Our results suggested that hMSCs incurred senescence upon IFN-α stimulation, while PML levels were observed significant increased. The recombinant lentiviral vector, which encodes shRNA against PML or full-length PML cDNA, was constructed. By knocking-down and overexpressing PML, we found that PML was indispensable to IFN-α mediated hMSC senescence. The molecular mechanism underlying this process may be an increased co-localization of PML and p53 induced by IFN-α. Our data demonstrated that IFN-α can induce cellular senescence of hMSCs and PML plays a key role in this process. These findings provided novel insight into the effect of IFN-α on hMSCs.
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Fu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China.
authors.forename: Jieping
authors.initials: J
authors.lastname: Wei
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou 310022, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China.
authors.forename: Binsheng
authors.initials: B
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China.
authors.forename: Yebo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Lai
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000071156:Promyelocytic Leukemia Protein; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D016898:Interferon-alpha; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human