Hepcidin regulation in a mouse model of acute hypoxia

Objective During hypoxia, hepcidin expression is inhibited to allow iron mobilization to sustain erythropoietic expansion. We analyzed molecular mechanisms underlying hypoxia‐induced hepcidin inhibition in an in vivo model of acute hypoxia. Methods Mice were kept under normal or hypoxic conditions f...

Full description

Saved in:
Bibliographic Details
Published in:European journal of haematology 2018-06, Vol.100 (6), p.636-643
Main Authors: Ravasi, Giulia, Pelucchi, Sara, Buoli Comani, Gaia, Greni, Federico, Mariani, Raffaella, Pelloni, Irene, Bombelli, Silvia, Perego, Roberto, Barisani, Donatella, Piperno, Alberto
Format: Article
Language:English
Subjects:
Bone marrow
erythroferrone
Erythropoiesis
Growth factors
Hepcidin
Hypoxia
Iron
Liver
Molecular modelling
mRNA
PDGF‐BB
Platelet-derived growth factor
Spleen
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objective During hypoxia, hepcidin expression is inhibited to allow iron mobilization to sustain erythropoietic expansion. We analyzed molecular mechanisms underlying hypoxia‐induced hepcidin inhibition in an in vivo model of acute hypoxia. Methods Mice were kept under normal or hypoxic conditions for 6 hours and 15 hours and treated with α‐PDGF‐BB antibody or PDGF‐BB receptor inhibitor. Blood, liver, spleen, and bone marrow were collected to extract RNA and protein or to quantify EPO and PDGF‐BB. mRNA and protein levels were assessed by RT‐PCR and Western blot. Results Hepcidin was strongly inhibited at 15 hours, and this downregulation followed erythropoiesis activation and upregulation of several growth factors. PDGF‐BB, erythroferrone, GDF15, and TWSG1 were upregulated by hypoxia in the bone marrow, but not in spleen or liver. Inactivation of PDGF‐BB or its receptor suppressed the hypoxia‐induced hepcidin inhibition. Conclusion Spleen and liver are not involved in the early stages of hypoxia‐induced hepcidin downregulation. Our data support the role of PDGF‐BB and probably also of erythroferrone in the recruitment of iron for erythropoiesis in the hypoxia setting. The rapid normalization of all the erythroid factors against persistent hepcidin suppression suggests that other signals are involved that should be clarified in future studies.
ISSN:0902-4441
1600-0609
DOI:10.1111/ejh.13062