The hepatokine FGL1 regulates hepcidin and iron metabolism during anemia in mice by antagonizing BMP signaling

被引：8

作者：

Sardo, Ugo ^{[1
]}

Perrier, Prunelle ^{[1
]}

Cormier, Kevin ^{[1
]}

Sotin, Manon ^{[1
]}

Personnaz, Jean ^{[1
]}

Medjbeur, Thanina ^{[1
]}

Desquesnes, Aurore ^{[1
]}

Cannizzo, Lisa ^{[1
]}

Ruiz-Martinez, Marc ^{[2
]}

Thevenin, Julie ^{[1
]}

Billore, Benjamin ^{[1
]}

Jung, Grace ^{[3
]}

Abboud, Elise ^{[4
]}

Peyssonnaux, Carole ^{[5
]}

Nemeth, Elizabeta ^{[3
]}

Ginzburg, Yelena Z. ^{[2
]}

Ganz, Tomas ^{[3
,6
]}

Kautz, Leon ^{[1
,7
]}

机构：

[1] Univ Toulouse, Inst Rech Sante Digest, INSERM, INRAE,ENVT,Univ Toulouse Paul Sabatier 3, Toulouse, France

[2] Icahn Sch Med Mt Sinai Hosp, New York, NY USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA

[4] Univ Paris, Inst Cochin, CNRS, INSERM, Paris, France

[5] Lab Excellence GR Ex, Paris, France

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA USA

[7] Univ Toulouse, INSERM, CHU Purpan, Inst Rech Sante Digest,U1220, Pl Docteur Baylac, F-31024 Toulouse, France

来源：

BLOOD | 2024年 / 143卷 / 13期

基金：

欧盟地平线“2020”; 美国国家卫生研究院; 欧洲研究理事会;

关键词：

ERYTHROFERRONE CONTRIBUTES; GENE-EXPRESSION; ERYTHROID REGULATOR; MOLECULAR-CLONING; MOUSE MODEL; LIVER; PROTEIN; HEPASSOCIN; MURINE; IDENTIFICATION;

D O I：

10.1182/blood.2023022724

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1282 / 1292

页数：11

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