Heme oxygenase‐1 protects bone marrow mesenchymal stem cells from iron overload through decreasing reactive oxygen species and promoting IL‐10 generation
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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DOI:
10.1016/j.yexcr.2017.10.029
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发表时间:
2018
影响因子:
3.7
通讯作者:
Zheng Y. Yu;D. Ma;Zhengchang He;Ping Liu;Jun Huang;Q. Fang;Jiangyuan Zhao;Ji S Wang
中科院分区:
文献类型:
--
作者:
Zheng Y. Yu;D. Ma;Zhengchang He;Ping Liu;Jun Huang;Q. Fang;Jiangyuan Zhao;Ji S Wang
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.