The hepatokine FGL1 regulates hepcidin and iron metabolism during anemia in mice by antagonizing BMP signaling
Year: 2024
Type: article
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 the adequate supply of iron to the bone marrow for red blood cell production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine fibrinogen-like 1 (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 higher hepcidin levels at baseline and after bleeding. FGL1 exerts its activity by directly binding to bone morphogenetic protein 6 (BMP6), thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription.
Source: Blood
Institutions: Université Toulouse III - Paul Sabatier, Inserm, École Nationale Vétérinaire de Toulouse, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Institut de Recherche en Santé Digestive, Université de Toulouse, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, University of California, Los Angeles, Centre National de la Recherche Scientifique, Université Paris Cité, Laboratory of Excellence GR-Ex, Institut Cochin
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Novo Nordisk, Akebia Therapeutics, National Institutes of Health, American Regent, National Institute of Diabetes and Digestive and Kidney Diseases, H2020 European Research Council
Awards: Functional characterization of erythroferrone and therapeutic applications, G304773848, G434337789, Biogenèse et pathologies du globule rouge, G4774453313, G4866930200, MECHANISM OF ACTION OF ERYTHROFERRONE AND PATHOLOGICAL IMPLICATIONS, Molecular pathophysiology of iron homeostasis during anemia and targeted intervention, Université Sorbonne Paris Cité, Investigating the regulation of iron homeostasis by erythroferrone and therapeutic applications, G8965471547, Regulatory Role of Transferrin in Erythropoiesis and Iron Metabolism, The Role of Erythroferrone in Regulating Bone Metabolism in Beta-Thalassemia
OpenAlex ID: W4390935909