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Charlebois, E.* ; Fillebeen, C.* ; Katsarou, A.* ; Rabinovich, A.* ; Wisniewski, K.* ; Venkataramani, V.* ; Michalke, B. ; Velentza, A.* ; Pantopoulos, K.*

A crosstalk between hepcidin and IRE/IRP pathways controls ferroportin expression and determines serum iron levels in mice.

eLife 11:e81332 (2022)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The iron hormone hepcidin is transcriptionally activated by iron or inflammation via distinct, partially overlapping pathways. We addressed how iron affects inflammatory hepcidin levels and the ensuing hypoferremic response. Dietary iron overload did not mitigate hepcidin induction in LPS-treated wt mice but prevented effective inflammatory hypoferremia. Likewise, LPS modestly decreased serum iron in hepcidin-deficient Hjv-/- mice, model of hemochromatosis. Synthetic hepcidin triggered hypoferremia in control but not iron-loaded wt animals. Furthermore, it dramatically decreased hepatic and splenic ferroportin in Hjv-/- mice on standard or iron-deficient diet, but only triggered hypoferremia in the latter. Mechanistically, iron antagonized hepcidin responsiveness by inactivating IRPs in the liver and spleen, to stimulate ferroportin mRNA translation. Prolonged LPS treatment eliminating ferroportin mRNA permitted hepcidin-mediated hypoferremia in iron-loaded mice. Thus, de novo ferroportin synthesis is critical determinant of serum iron and finetunes hepcidin-dependent functional outcomes. Our data uncover a crosstalk between hepcidin and IRE/IRP systems that controls tissue ferroportin expression and determines serum iron levels. Moreover, they suggest that hepcidin supplementation therapy is more efficient combined with iron depletion.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cell Biology ; Immunology ; Inflammation ; Mouse
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 11, Heft: , Seiten: , Artikelnummer: e81332 Supplement: ,
Verlag eLife Sciences Publications
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical BioGeoChemistry (BGC)
Förderungen Deutsche Forschungsgemeinschaft
CIHR