title: EPO-dependent induction of erythroferrone drives hepcidin suppression and systematic iron absorption under phenylhydrazine-induced hemolytic anemia.
abstract: Hemolytic anemia is a common form of anemia due to hemolysis, resulting in disordered iron homeostasis. In this study, a dose of 40mg/kg phenylhydrazine (PHZ) was injected into mice to successfully establish a pronounced anemia animal model, which resulted in stress erythropoiesis and iron absorption. We found that serum erythropoietin (EPO) concentration was dramatically elevated by nearly 5000-fold for the first 2days, and then drop to the basal level on day 6 after PHZ injection. Mirrored with serum EPO concentration, the mRNA expression of erythroferrone (ERFE) was rapidly increased in the bone marrow and spleen 3days after injection of PHZ, and then gradually decreased but was still higher than baseline on day 6. In addition, we also found that the hepcidin mRNA levels were gradually reduced almost up to 8-fold on day 5, and then was ameliorated compared to the untreated control. Mechanistic investigation manifested that the increase of serum EPO essentially determined the induction of ERFE expression particular at the first 3days after PHZ treatment. Lentiviral mediated ERFE knockdown significantly restrained hepcidin suppression under PHZ treatment. Thus, our data unearthed EPO-dependent ERFE expression acts as an erythropoiesis-driven regulator of iron metabolism under PHZ-induced hemolytic anemia.
authors.affiliation: Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
authors.forename: Xingkang
authors.initials: X
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Environment Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China; State Key Laboratory of Environment Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Environment Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Environment Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China. Electronic address: drzhangzhihong@163.com.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China. Electronic address: yongxu2012@yahoo.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000743:Anemia, Hemolytic / Q000097:blood / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004920:Erythropoiesis; D004921:Erythropoietin / Q000097:blood / Q000378:metabolism*; D006461:Hemolysis; D064451:Hepcidins / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D010659:Phenylhydrazines; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C572502:Erfe protein, mouse; D064451:Hepcidins; D009124:Muscle Proteins; D010659:Phenylhydrazines; D012333:RNA, Messenger; C030299:phenylhydrazine; D004921:Erythropoietin; D007501:Iron
keywords: Erythroferrone; Erythropoietin; Hemolysis; Hepcidin; Iron