Department of Hematology, Affiliated Hospital of Guizhou Medical University, PR China; Hematological Institute of Guizhou Province, PR China; Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Centre, PR China.
Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, PR China.
Exp Cell Res. 2018 Jan 1;362(1):28-42. doi: 10.1016/j.yexcr.2017.10.029. Epub 2017 Oct 28.
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.
铁过载（IO）是由血液系统疾病中的频繁输血引起的，已成为主要关注点。在本研究中，在 IO 早期观察到骨髓间充质干细胞（BMMSCs）中血红素加氧酶-1（HO-1）的上调，这对 IO 小鼠模型具有良好的预后。鉴于 HO-1 在 IO 损伤的 BMMSCs 中的保护作用尚不清楚，因此在体外和体内探索了其机制。体外转染 HO-1/siHO-1 后，建立了小鼠模型以进一步评估 HO-1 对体内 IO 的影响。结果表明，HO-1 通过减少细胞内活性氧（ROS）并增加 IL-10 分泌来降低 IO 时 BMMSCs 的凋亡率。此外，IL-10 是由 HO-1 通过 ERK 途径介导的。铁调素通过 IL-10 下调细胞内铁。总之，HO-1 通过在铁过载时分泌 IL-10 来保护 BMMSCs 免受 ROS 损伤。
