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

详细信息    查看全文

• 作者：Xingkang Jiang^a ; Ming Gao^b ; Yue Chen^a ; ^b ; Jing Liu^b ; Shiyong Qi^a ; Juan Ma^b ; Zhihong Zhang^a ; ^{drzhangzhihong@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yong Xu^a ; ^{yongxu2012@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PHZ ; phenylhydrazine ; ERFE ; erythroferrone ; EPO ; erythropoietin ; FAC ; Ferric Ammonium Citrate ; RBC ; red blood cells ; HGB ; hemoglobin ; MCV ; mean corpuscular volume ; MCH ; mean corpuscular hemoglobin
• 刊名：Blood Cells, Molecules and Diseases
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：58
• 期：Complete
• 页码：45-51
• 全文大小：842 K

文摘

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.