The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Preprints, Working Papers, ... Year : 2023

The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice

Abstract

ABSTRACT As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure adequate supply of iron to the bone marrow for red blood cells production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine FGL1 as a previously undescribed suppressor of hepcidin that is induced in the liver in response to hypoxia during the recovery from anemia and in thalassemic mice. We demonstrated that FGL1 is a potent suppressor of hepcidin in vitro and in vivo . Deletion of Fgl1 in mice results in a blunted repression of hepcidin after bleeding. FGL1 exerts its activity by direct binding to BMP6, thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription. Key points 1/ FGL1 regulates iron metabolism during the recovery from anemia. 2/ FGL1 is an antagonist of the BMP/SMAD signaling pathway.
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hal-04444239 , version 1 (07-02-2024)

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Ugo Sardo, Prunelle Perrier, Kevin Cormier, Manon Sotin, Aurore Desquesnes, et al.. The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice. 2024. ⟨hal-04444239⟩
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