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

2.

Camaschella

C

.

Iron deficiency

.

Blood

.

2019

;

133

(

1

):

30

-

39

.

3.

Finch

C

.

Regulators of iron balance in humans

.

Blood

.

1994

;

84

(

6

):

1697

-

1702

.

4.

Nemeth

E

,

Tuttle

MS

,

Powelson

J

, et al.

Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization

.

Science

.

2004

;

306

(

5704

):

2090

-

2093

.

5.

Aschemeyer

S

,

Qiao

B

,

Stefanova

D

, et al.

Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin

.

Blood

.

2018

;

131

(

8

):

899

-

910

.

6.

Koch

PS

,

Olsavszky

V

,

Ulbrich

F

, et al.

Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis

.

Blood

.

2017

;

129

(

4

):

415

-

419

.

7.

Meynard

D

,

Kautz

L

,

Darnaud

V

,

Canonne-Hergaux

F

,

Coppin

H

,

Roth

MP

.

Lack of the bone morphogenetic protein BMP6 induces massive iron overload

.

Nat Genet

.

2009

;

41

(

4

):

478

-

481

.

8.

Andriopoulos

B

,

Corradini

E

,

Xia

Y

, et al.

BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism

.

Nat Genet

.

2009

;

41

(

4

):

482

-

487

.

9.

Wang

CY

,

Babitt

JL

.

Liver iron sensing and body iron homeostasis

.

Blood

.

2019

;

133

(

1

):

18

-

29

.

10.

Kautz

L

,

Jung

G

,

Nemeth

E

,

Ganz

T

.

Erythroferrone contributes to recovery from anemia of inflammation

.

Blood

.

2014

;

124

(

16

):

2569

-

2574

.

11.

Kautz

L

,

Jung

G

,

Valore

EV

,

Rivella

S

,

Nemeth

E

,

Ganz

T

.

Identification of erythroferrone as an erythroid regulator of iron metabolism

.

Nat Genet

.

2014

;

46

(

7

):

678

-

684

.

12.

Ganz

T

,

Jung

G

,

Naeim

A

, et al.

Immunoassay for human serum erythroferrone

.

Blood

.

2017

;

130

(

10

):

1243

-

1246

.

13.

Bondu

S

,

Alary

AS

,

Lefevre

C

, et al.

A variant erythroferrone disrupts iron homeostasis in SF3B1-mutated myelodysplastic syndrome

.

Sci Transl Med

.

2019

;

11

(

500

):

eaav5467

.

14.

Russo

R

,

Andolfo

I

,

Manna

F

, et al.

Increased levels of ERFE-encoding FAM132B in patients with congenital dyserythropoietic anemia type II

.

Blood

.

2016

;

128

(

14

):

1899

-

1902

.

15.

Arezes

J

,

Foy

N

,

McHugh

K

, et al.

Erythroferrone inhibits the induction of hepcidin by BMP6

.

Blood

.

2018

;

132

(

14

):

1473

-

1477

.

16.

Kautz

L

,

Jung

G

,

Du

X

, et al.

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of beta-thalassemia

.

Blood

.

2015

;

126

(

17

):

2031

-

2037

.

17.

Arezes

J

,

Foy

N

,

McHugh

K

, et al.

Antibodies against the erythroferrone N-terminal domain prevent hepcidin suppression and ameliorate murine thalassemia

.

Blood

.

2020

;

135

(

8

):

547

-

557

.

18.

Tanno

T

,

Bhanu

NV

,

Oneal

PA

, et al.

High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin

.

Nat Med

.

2007

;

13

(

9

):

1096

-

1101

.

19.

Tanno

T

,

Porayette

P

,

Sripichai

O

, et al.

Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells

.

Blood

.

2009

;

114

(

1

):

181

-

186

.

20.

Tanno

T

,

Noel

P

,

Miller

JL

.

Growth differentiation factor 15 in erythroid health and disease

.

Curr Opin Hematol

.

2010

;

17

(

3

):

184

-

190

.

21.

Casanovas

G

,

Vujic Spasic

M

,

Casu

C

, et al.

The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice

.

Haematologica

.

2013

;

98

(

3

):

444

-

447

.

22.

Hara

H

,

Yoshimura

H

,

Uchida

S

, et al.

Molecular cloning and functional expression analysis of a cDNA for human hepassocin, a liver-specific protein with hepatocyte mitogenic activity

.

Biochim Biophys Acta

.

2001

;

1520

(

1

):

45

-

53

.

23.

Yamamoto

T

,

Gotoh

M

,

Sasaki

H

,

Terada

M

,

Kitajima

M

,

Hirohashi

S

.

Molecular cloning and initial characterization of a novel fibrinogen-related gene, HFREP-1

.

Biochem Biophys Res Commun

.

1993

;

193

(

2

):

681

-

687

.

24.

Demchev

V

,

Malana

G

,

Vangala

D

, et al.

Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization

.

PLoS One

.

2013

;

8

(

3

):

e58084

.

25.

Rijken

DC

,

Dirkx

SP

,

Luider

TM

,

Leebeek

FW

.

Hepatocyte-derived fibrinogen-related protein-1 is associated with the fibrin matrix of a plasma clot

.

Biochem Biophys Res Commun

.

2006

;

350

(

1

):

191

-

194

.

26.

Peyssonnaux

C

,

Zinkernagel

AS

,

Schuepbach

RA

, et al.

Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)

.

J Clin Invest

.

2007

;

117

(

7

):

1926

-

1932

.

27.

Hanudel

MR

,

Wong

S

,

Jung

G

, et al.

Amelioration of chronic kidney disease-associated anemia by vadadustat in mice is not dependent on erythroferrone

.

Kidney Int

.

2021

;

100

(

1

):

79

-

89

.

28.

Kautz

L

,

Meynard

D

,

Monnier

A

, et al.

Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver

.

Blood

.

2008

;

112

(

4

):

1503

-

1509

.

29.

Liu

Z

,

Ukomadu

C

.

Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant

.

Biochem Biophys Res Commun

.

2008

;

365

(

4

):

729

-

734

.

30.

Bothwell

TH

,

Pirzio-Biroli

G

,

Finch

CA

.

Iron absorption. I. Factors influencing absorption

.

J Lab Clin Med

.

1958

;

51

(

1

):

24

-

36

.

31.

Finch

CA

.

Erythropoiesis, erythropoietin, and iron

.

Blood

.

1982

;

60

(

6

):

1241

-

1246

.

32.

Hanudel

MR

,

Rappaport

M

,

Chua

K

, et al.

Levels of the erythropoietin-responsive hormone erythroferrone in mice and humans with chronic kidney disease

.

Haematologica

.

2018

;

103

(

4

):

e141

-

e142

.

33.

Latour

C

,

Wlodarczyk

MF

,

Jung

G

, et al.

Erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia

.

Haematologica

.

2017

;

102

(

1

):

60

-

68

.

34.

Artuso

I

,

Pettinato

M

,

Nai

A

, et al.

Transient decrease of serum iron after acute erythropoietin treatment contributes to hepcidin inhibition by ERFE in mice

.

Haematologica

.

2019

;

104

(

3

):

e87

-

e90

.

35.

Mirciov

CSG

,

Wilkins

SJ

,

Hung

GCC

,

Helman

SL

,

Anderson

GJ

,

Frazer

DM

.

Circulating iron levels influence the regulation of hepcidin following stimulated erythropoiesis

.

Haematologica

.

2018

;

103

(

10

):

1616

-

1626

.

36.

Coffey

R

,

Sardo

U

,

Kautz

L

, et al.

Erythroferrone is not required for the glucoregulatory and hematologic effects of chronic erythropoietin treatment in mice

.

Physiol Rep

.

2018

;

6

(

19

):

e13890

.

37.

Baze

MM

,

Schlauch

K

,

Hayes

JP

.

Gene expression of the liver in response to chronic hypoxia

.

Physiol Genomics

.

2010

;

41

(

3

):

275

-

288

.

38.

Elvidge

GP

,

Glenny

L

,

Appelhoff

RJ

,

Ratcliffe

PJ

,

Ragoussis

J

,

Gleadle

JM

.

Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways

.

J Biol Chem

.

2006

;

281

(

22

):

15215

-

15226

.

39.

Talens

S

,

Leebeek

FW

,

Demmers

JA

,

Rijken

DC

.

Identification of fibrin clot-bound plasma proteins

.

PLoS One

.

2012

;

7

(

8

):

e41966

.

40.

Latour

C

,

Kautz

L

,

Besson-Fournier

C

, et al.

Testosterone perturbs systemic iron balance through activation of epidermal growth factor receptor signaling in the liver and repression of hepcidin

.

Hepatology

.

2014

;

59

(

2

):

683

-

694

.

41.

Petersen

MA

,

Ryu

JK

,

Chang

KJ

, et al.

Fibrinogen activates BMP signaling in oligodendrocyte progenitor cells and inhibits remyelination after vascular damage

.

Neuron

.

2017

;

96

(

5

):

1003

-

1012.e7

.

42.

Pous

L

,

Deshpande

SS

,

Nath

S

, et al.

Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling

.

Nat Commun

.

2020

;

11

(

1

):

630

.

43.

Srole

DN

,

Jung

G

,

Waring

AJ

,

Nemeth

E

,

Ganz

T

.

Characterization of erythroferrone structural domains relevant to its iron-regulatory function

.

J Biol Chem

.

2023

;

299

(

12

):

105374

.

44.

Coffey

R

,

Jung

G

,

Olivera

JD

, et al.

Erythroid overproduction of erythroferrone causes iron overload and developmental abnormalities in mice

.

Blood

.

2022

;

139

(

3

):

439

-

451

.

45.

Pasricha

SR

,

Lim

PJ

,

Duarte

TL

, et al.

Hepcidin is regulated by promoter-associated histone acetylation and HDAC3

.

Nat Commun

.

2017

;

8

(

1

):

403

.

46.

Frydlova

J

,

Rogalsky

DW

,

Truksa

J

,

Necas

E

,

Vokurka

M

,

Krijt

J

.

Effect of stimulated erythropoiesis on liver SMAD signaling pathway in iron-overloaded and iron-deficient mice

.

PLoS One

.

2019

;

14

(

4

):

e0215028

.

47.

Ramos

E

,

Kautz

L

,

Rodriguez

R

, et al.

Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice

.

Hepatology

.

2011

;

53

(

4

):

1333

-

1341

.

48.

Latour

C

,

Besson-Fournier

C

,

Meynard

D

, et al.

Differing impact of the deletion of hemochromatosis-associated molecules HFE and transferrin receptor-2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin

.

Hepatology

.

2016

;

63

(

1

):

126

-

137

.

49.

Ben-Moshe

S

,

Shapira

Y

,

Moor

AE

, et al.

Spatial sorting enables comprehensive characterization of liver zonation

.

Nat Metab

.

2019

;

1

(

9

):

899

-

911

.

50.

Kietzmann

T

.

Liver zonation in health and disease: hypoxia and hypoxia-inducible transcription factors as concert masters

.

Int J Mol Sci

.

2019

;

20

(

9

):

2347

.

51.

Trefts

E

,

Gannon

M

,

Wasserman

DH

.

The liver

.

Curr Biol

.

2017

;

27

(

21

):

R1147

-

R1151

.

52.

Wu

HT

,

Lu

FH

,

Ou

HY

, et al.

The role of hepassocin in the development of non-alcoholic fatty liver disease

.

J Hepatol

.

2013

;

59

(

5

):

1065

-

1072

.

53.

Huang

RL

,

Li

CH

,

Du

YF

, et al.

Discovery of a role of the novel hepatokine, hepassocin, in obesity

.

Biofactors

.

2020

;

46

(

1

):

100

-

105

.

54.

Ou

HY

,

Wu

HT

,

Lin

CH

, et al.

the hepatic protection effects of hepassocin in hyperglycemic crisis

.

J Clin Endocrinol Metab

.

2017

;

102

(

7

):

2407

-

2415

.

55.

Wang

J

,

Sanmamed

MF

,

Datar

I

, et al.

Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3

.

Cell

.

2019

;

176

(

1-2

):

334

-

347.e12

.

56.

Lehtio

J

,

Arslan

T

,

Siavelis

I

, et al.

Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune evasion mechanisms

.

Nat Cancer

.

2021

;

2

(

11

):

1224

-

1242

.

57.

Zhang

Y

,

Qiao

HX

,

Zhou

YT

,

Hong

L

,

Chen

JH

.

Fibrinogen-like-protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis

.

Mol Med Rep

.

2018

;

18

(

2

):

1465

-

1472

.

58.

Lv

Z

,

Cui

B

,

Huang

X

, et al.

FGL1 as a novel mediator and biomarker of malignant progression in clear cell renal cell carcinoma

.

Front Oncol

.

2021

;

11

:

756843

.

59.

Saito

T

,

Ji

G

,

Shinzawa

H

, et al.

Genetic variations in humans associated with differences in the course of hepatitis C

.

Biochem Biophys Res Commun

.

2004

;

317

(

2

):

335

-

341

.