The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells

Fu,Shan; Wei,Jieping; Wang,Gang; Wang,Binsheng; Wang,Yebo; Lai,Xiaoyu; Huang,He

doi:10.3892/ijo.2014.2738

The key role of PML in IFN-α induced cellular senescence of human mesenchymal stromal cells

Authors:
- Shan Fu
- Jieping Wei
- Gang Wang
- Binsheng Wang
- Yebo Wang
- Xiaoyu Lai
- He Huang
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Affiliations: Bone Marrow Transplantation Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310003, P.R. China, Zhejiang Cancer Hospital, Hangzhou 310022, P.R. China
Published online on: October 30, 2014 https://doi.org/10.3892/ijo.2014.2738
Pages: 351-359

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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.

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