EPO-dependent induction of erythroferrone drives hepcidin suppression and systematic iron absorption under phenylhydrazine-induced hemolytic anemia

被引：33

作者：

Jiang, Xingkang ^{[1
]}

Gao, Ming ^{[2
]}

Chen, Yue ^{[1
,2
]}

Liu, Jing ^{[2
]}

Qi, Shiyong ^{[1
]}

Ma, Juan ^{[2
]}

Zhang, Zhihong ^{[1
]}

Xu, Yong ^{[1
]}

机构：

[1] Tianjin Med Univ, Tianjin Inst Urol, Hosp 2, Dept Urol, Pingjiang Rd 32, Tianjin 300211, Peoples R China

[2] Chinese Acad Sci, State Key Lab Environm Chem & Ecotoxicol, Res Ctr Ecoenvironm Sci, Beijing 100085, Peoples R China

来源：

BLOOD CELLS MOLECULES AND DISEASES | 2016年 / 58卷

基金：

中国国家自然科学基金;

关键词：

Etythropoietin; Erythroferrone; Hemolysis; Hepcidin; Iron; ERYTHROID REGULATOR; EXPRESSION; IDENTIFICATION; CONTRIBUTES; METABOLISM; MODEL; MICE; 2ND;

D O I：

10.1016/j.bcmd.2016.02.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hemolytic anemia is a common form of anemia due to hemolysis, resulting in disordered iron homeostasis. In this study, a dose of 40 mg/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 2 days, 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 3 days 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 3 days 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. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：45 / 51

页数：7