Heme oxygenase-1 protects bone marrow mesenchymal stem cells from iron overload through decreasing reactive oxygen species and promoting IL-10 generation

被引:42
作者
Yu, Zheng Y. [1 ,2 ,3 ]
Ma, Dan [1 ,2 ,3 ]
He, Zheng C. [1 ,2 ,3 ]
Liu, Ping [1 ,2 ,3 ]
Huang, Jun [1 ,2 ,3 ]
Fang, Qin [4 ]
Zhao, Jiang Y. [1 ,2 ,3 ]
Wang, Ji S. [1 ,2 ,3 ]
机构
[1] Guizhou Med Univ, Affiliated Hosp, Dept Hematol, Guiyang 550004, Guizhou, Peoples R China
[2] Hematol Inst Guizhou Prov, Guiyang, Guizhou, Peoples R China
[3] Guizhou Prov Lab Hematopoiet Stem Cell Transplant, Guiyang, Guizhou, Peoples R China
[4] Guizhou Med Univ, Affiliated Hosp, Dept Pharm, Guiyang, Guizhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Iron overload; Heme oxygenase-1; Interleukin; 10; Reactive oxygen species; Bone marrow mesenchymal stem cells; ERK pathway; CHRONIC MYELOID-LEUKEMIA; INTERLEUKIN-10; IL-10; BETA-THALASSEMIA; SIGNALING PATHWAY; CHELATION-THERAPY; OXIDATIVE STRESS; GENE-EXPRESSION; CRUCIAL ROLE; DEFEROXAMINE; HEMATOPOIESIS;
D O I
10.1016/j.yexcr.2017.10.029
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 10 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 10 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 ERIC 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.
引用
收藏
页码:28 / 42
页数:15
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