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Hepcidin regulation in a mouse model of acute hypoxia
Author(s) -
Ravasi Giulia,
Pelucchi Sara,
Buoli Comani Gaia,
Greni Federico,
Mariani Raffaella,
Pelloni Irene,
Bombelli Silvia,
Perego Roberto,
Barisani Donatella,
Piperno Alberto
Publication year - 2018
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13062
Subject(s) - hepcidin , erythropoiesis , downregulation and upregulation , hypoxia (environmental) , spleen , endocrinology , medicine , western blot , bone marrow , ineffective erythropoiesis , platelet derived growth factor receptor , receptor , biology , chemistry , growth factor , inflammation , anemia , biochemistry , organic chemistry , oxygen , gene
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, GDF 15, and TWSG 1 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.