Heme oxygenase-1 protects bone marrow mesenchymal stem cells from iron overload through decreasing reactive oxygen species and promoting IL-10 generation |
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| Authors: | Zheng Y. Yu Dan Ma Zheng C. He Ping Liu Jun Huang Qin Fang Jiang Y. Zhao Ji S. Wang |
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| Affiliation: | 1. Department of Hematology, Affiliated Hospital of Guizhou Medical University, PR China;2. Hematological Institute of Guizhou Province, PR China;3. Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Centre, PR China;4. Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, PR China |
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| Abstract: | Iron overload (IO) caused by frequent blood transfusion in hematological diseases has become a major concern. In this study, up-regulation of heme oxygenase-1 (HO-1), a protector against oxidative stress, was observed in bone marrow mesenchymal stem cells (BMMSCs) at the early stage of IO and had favorable prognosis in an IO mouse model. Given that the protective role of HO-1 in IO damage of BMMSCs was still unknown, the mechanism was explored in vitro and in vivo. BMMSCs were transfected with HO-1/siHO-1 in vitro, and the mouse model was established to further evaluate the effect of HO-1 on IO in vivo. As a result, HO-1 decreased the apoptotic rate of BMMSCs with IO through reducing intracellular reactive oxygen species (ROS) but increasing IL-10 secretion. In addition, IL-10 was mediated by HO-1 via the ERK pathway. Intracellular iron was down-regulated by hepcidin depending on IL-10. In conclusion, HO-1 protects BMMSCs from ROS by secreting IL-10 upon iron overload. |
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| Keywords: | Iron overload Heme oxygenase-1 Interleukin 10 Reactive oxygen species Bone marrow mesenchymal stem cells ERK pathway |
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