Recombinant human erythropoietin-induced erythropoiesis regulates hepcidin expression over iron status in the rat

被引：8

作者：

Ribeiro, Sandra ^{[1
]}

Garrido, Patricia ^{[2
]}

Fernandes, Joao ^{[2
,3
]}

Rocha, Susana ^{[1
]}

Rocha-Pereira, Petronila ^{[1
,4
]}

Costa, Elisio ^{[1
]}

Belo, Luis ^{[1
]}

Reis, Flavio ^{[2
,3
]}

Santos-Silva, Alice ^{[1
]}

机构：

[1] Univ Porto, Fac Pharm, Dept Biol Sci,Lab Biochem, Res Unit Appl Mol Biosci UCIBIO,REQUIMTE, P-4050313 Oporto, Portugal

[2] Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci IBILI, Lab Pharmacol & Expt Therapeut, Coimbra, Portugal

[3] Univ Coimbra, Inst Biomed Imaging & Life Sci CNCIBILI Res Unit, Ctr Neurosci & Cell Biol, Coimbra, Portugal

[4] Univ Beira Interior, Fac Hlth Sci, Hlth Sci Res Ctr, Covilha, Portugal

来源：

BLOOD CELLS MOLECULES AND DISEASES | 2016年 / 59卷

关键词：

Erythropoiesis; Hepcidin; Iron; Matriptase-2; Transferrin saturation; ERYTHROID REGULATOR; BETA-THALASSEMIA; METABOLISM; ERYTHROFERRONE; IDENTIFICATION; MODEL;

D O I：

10.1016/j.bcmd.2016.04.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The crosstalk between several factors controlling hepcidin synthesis is poorly clarified for different physiological and pathological conditions. Our aim was to study the impact of increasing recombinant human erythropoietin (rHuEPO) doses on erythropoiesis, iron metabolism and hepcidin, using a rat model. Male Wistar rats were divided in 5 groups: control (vehicle) and rHuEPO-treated groups (100, 200, 400 and 600 IU/kg body weight/week), 3 times per week, during 3 weeks. Hematological and iron data were evaluated. The expression of several genes involved in iron metabolism was analyzed by qPCR. Liver hepcidin protein was evaluated byWestern Blot. The rHuEPO treatment induced erythropoiesis and increased transferrin saturation (TSAT) in a dose dependent manner. Tf receptor 2 (TfR2), hemojuvelin (HJV) and bone morphogenetic protein 6 (BMP6) were upregulated in rHuEPO200 group. Matriptase-2 was down-regulated in rHuEPO200 group, and up-regulated in the other rHuEPO-treated groups. Hepcidin synthesis was increased in rHuEPO200 group, and repressed in the rHuEPO400 and rHuEPO600 groups. Our study showed that when a high erythropoietic stimulus occurs, hepcidin synthesis is mainly regulated by TSAT; however, when the erythropoiesis rate reaches a specific threshold, extramedullary hematopoiesis is triggered, and the control of hepcidin synthesis is switched to matriptase-2, thus inhibiting hepcidin synthesis. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：63 / 70

页数：8

共 30 条

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