Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2

Erythropoietin (EPO) downregulates hepcidin expression to increase the availability of iron; the downregulation of hepcidin is mediated by erythroferrone (ERFE) secreted by erythroblasts. Erythroblasts also express transferrin receptor 2 (TFR2); however, the possible role of TFR2 in hepcidin downreg...

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Main Authors: Betty Berezovsky, Martin Báječný, Jana Frýdlová, Iuliia Gurieva, Daniel Wayne Rogalsky, Petr Přikryl, Vít Pospíšil, Emanuel Nečas, Martin Vokurka, Jan Krijt
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/15/8209
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author Betty Berezovsky
Martin Báječný
Jana Frýdlová
Iuliia Gurieva
Daniel Wayne Rogalsky
Petr Přikryl
Vít Pospíšil
Emanuel Nečas
Martin Vokurka
Jan Krijt
author_facet Betty Berezovsky
Martin Báječný
Jana Frýdlová
Iuliia Gurieva
Daniel Wayne Rogalsky
Petr Přikryl
Vít Pospíšil
Emanuel Nečas
Martin Vokurka
Jan Krijt
author_sort Betty Berezovsky
collection DOAJ
description Erythropoietin (EPO) downregulates hepcidin expression to increase the availability of iron; the downregulation of hepcidin is mediated by erythroferrone (ERFE) secreted by erythroblasts. Erythroblasts also express transferrin receptor 2 (TFR2); however, the possible role of TFR2 in hepcidin downregulation is unclear. The purpose of the study was to correlate liver expression of hepcidin with the expression of ERFE and TFR2 in murine bone marrow and spleen at 4, 16, 24, 48, 72 and 96 h following administration of a single dose of EPO. Splenic <i>Fam132b</i> expression increased 4 h after EPO injection; liver hepcidin mRNA was decreased at 16 h. In the spleen, expression of TFR2 and transferrin receptor (TFR1) proteins increased by an order of magnitude at 48 and 72 h after EPO treatment. The EPO-induced increase in splenic TFR2 and TFR1 was associated with an increase in the number of <i>Tfr2</i>- and <i>Tfr1</i>-expressing erythroblasts. Plasma exosomes prepared from EPO-treated mice displayed increased amount of TFR1 protein; however, no exosomal TFR2 was detected. Overall, the results confirm the importance of ERFE in stress erythropoiesis, support the role of TFR2 in erythroid cell development, and highlight possible differences in the removal of TFR2 and TFR1 from erythroid cell membranes.
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spelling doaj.art-572a3dd4dd8340ccafce2a1d128a5e362023-11-22T05:44:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215820910.3390/ijms22158209Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2Betty Berezovsky0Martin Báječný1Jana Frýdlová2Iuliia Gurieva3Daniel Wayne Rogalsky4Petr Přikryl5Vít Pospíšil6Emanuel Nečas7Martin Vokurka8Jan Krijt9Institute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicInstitute of Pathophysiology, First Faculty of Medicine, Charles University, U Nemocnice 5, 128 53 Prague, Czech RepublicErythropoietin (EPO) downregulates hepcidin expression to increase the availability of iron; the downregulation of hepcidin is mediated by erythroferrone (ERFE) secreted by erythroblasts. Erythroblasts also express transferrin receptor 2 (TFR2); however, the possible role of TFR2 in hepcidin downregulation is unclear. The purpose of the study was to correlate liver expression of hepcidin with the expression of ERFE and TFR2 in murine bone marrow and spleen at 4, 16, 24, 48, 72 and 96 h following administration of a single dose of EPO. Splenic <i>Fam132b</i> expression increased 4 h after EPO injection; liver hepcidin mRNA was decreased at 16 h. In the spleen, expression of TFR2 and transferrin receptor (TFR1) proteins increased by an order of magnitude at 48 and 72 h after EPO treatment. The EPO-induced increase in splenic TFR2 and TFR1 was associated with an increase in the number of <i>Tfr2</i>- and <i>Tfr1</i>-expressing erythroblasts. Plasma exosomes prepared from EPO-treated mice displayed increased amount of TFR1 protein; however, no exosomal TFR2 was detected. Overall, the results confirm the importance of ERFE in stress erythropoiesis, support the role of TFR2 in erythroid cell development, and highlight possible differences in the removal of TFR2 and TFR1 from erythroid cell membranes.https://www.mdpi.com/1422-0067/22/15/8209hepcidinerythroferronetransferrin receptorexosomes
spellingShingle Betty Berezovsky
Martin Báječný
Jana Frýdlová
Iuliia Gurieva
Daniel Wayne Rogalsky
Petr Přikryl
Vít Pospíšil
Emanuel Nečas
Martin Vokurka
Jan Krijt
Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2
International Journal of Molecular Sciences
hepcidin
erythroferrone
transferrin receptor
exosomes
title Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2
title_full Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2
title_fullStr Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2
title_full_unstemmed Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2
title_short Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2
title_sort effect of erythropoietin on the expression of murine transferrin receptor 2
topic hepcidin
erythroferrone
transferrin receptor
exosomes
url https://www.mdpi.com/1422-0067/22/15/8209
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