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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Authors | Zheng Y Yu, Dan Ma, Zheng C He, Ping Liu, Jun Huang, Qin Fang, Jiang Y Zhao, Ji S Wang |
Journal | Experimental cell research
(Exp Cell Res)
Vol. 362
Issue 1
Pg. 28-42
(01 01 2018)
ISSN: 1090-2422 [Electronic] United States |
PMID | 29111167
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2017. Published by Elsevier Inc. |
Chemical References |
- Membrane Proteins
- Reactive Oxygen Species
- Interleukin-10
- Iron
- Heme Oxygenase-1
- Hmox1 protein, mouse
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Topics |
- Animals
- Bone Marrow Cells
(drug effects, metabolism, pathology)
- Cytoprotection
(drug effects, genetics)
- HEK293 Cells
- Heme Oxygenase-1
(genetics, physiology)
- Humans
- Interleukin-10
(metabolism)
- Iron
(toxicity)
- Iron Overload
(genetics, metabolism, prevention & control)
- Male
- Membrane Proteins
(genetics, physiology)
- Mesenchymal Stem Cells
(drug effects, metabolism, pathology)
- Mice
- Mice, Inbred C57BL
- Oxidative Stress
(drug effects, genetics)
- Reactive Oxygen Species
(metabolism)
- Transfection
- Up-Regulation
(drug effects, genetics)
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