Evidence map›Paper›PMID 37478395›Full record

ArticleBlood2023

BMP5 contributes to hepcidin regulation and systemic iron homeostasis in mice.

Xia Xiao, Yang Xu, Gillian A Moschetta, Yang Yu, Allison L Fisher, Víctor M Alfaro-Magallanes, Shasta McMillen, Sydney Phillips, Chia-Yu Wang, Jan Christian and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  2. TGF-β Pathway-Based Polygenic Risk Score Modifies the Association between Red Meat Intake and Colorectal Cancer Risk: Application of a Novel Pathway-Based PRS Method.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
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  15. [Advances in Molecular Regulatory Mechanisms of Jaw Repair and Reconstruction].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Xia XiaoNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-9874-5240
Yang XuNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Gillian A MoschettaNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Yang YuNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Allison L FisherNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Víctor M Alfaro-MagallanesNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-0456-1222
Shasta McMillenNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Sydney PhillipsNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.ORCID 0009-0002-3079-5978
Chia-Yu WangNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-3679-6453
Jan ChristianDivision of Hematology and Hematologic Malignancies, Department of Neurobiology and Internal Medicine, University of Utah, Salt Lake City, UT.ORCID 0000-0003-3812-3658
Jodie L BabittNephrology Division and Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Harvard University · USUniversity of Utah · US

Funding

Regulation of Iron Homeostasis by BMP SignalingR01DK087727 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BABITT, JODIE L · 2010 to 2024
$6.0M
BMP Ligands in Hepcidin RegulationR01DK128068 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BABITT, JODIE L, CHRISTIAN, JAN L · 2021 to 2024
$2.6M
NIDDK NIH HHS R01 DK087727NIDDK NIH HHS R01 DK128068
6 · The paper itself

Abstract

Hepcidin is the master regulator of systemic iron homeostasis. The bone morphogenetic protein (BMP) signaling pathway is a critical regulator of hepcidin expression in response to iron and erythropoietic drive. Although endothelial-derived BMP6 and BMP2 ligands have key functional roles as endogenous hepcidin regulators, both iron and erythropoietic drives still regulate hepcidin in mice lacking either or both ligands. Here, we used mice with an inactivating Bmp5 mutation (Bmp5se), either alone or together with a global or endothelial Bmp6 knockout, to investigate the functional role of BMP5 in hepcidin and systemic iron homeostasis regulation. We showed that Bmp5se-mutant mice exhibit hepcidin deficiency at age 10 days, blunted hepcidin induction in response to oral iron gavage, and mild liver iron loading when fed on a low- or high-iron diet. Loss of 1 or 2 functional Bmp5 alleles also leads to increased iron loading in Bmp6-heterozygous mice and more profound hemochromatosis in global or endothelial Bmp6-knockout mice. Moreover, double Bmp5- and Bmp6-mutant mice fail to induce hepcidin in response to long-term dietary iron loading. Finally, erythroferrone binds directly to BMP5 and inhibits BMP5 induction of hepcidin in vitro. Although erythropoietin suppresses hepcidin in Bmp5se-mutant mice, it fails to suppress hepcidin in double Bmp5- and Bmp6-mutant males. Together, these data demonstrate that BMP5 plays a functional role in hepcidin and iron homeostasis regulation, particularly under conditions in which BMP6 is limited.

Indexed as

HemochromatosisHepcidinsAnimalsBone Morphogenetic Protein 5Bone Morphogenetic Protein 6HomeostasisIronLiverMaleMiceMice, KnockoutBmp5 protein, mouseBone Morphogenetic Protein 5Bone Morphogenetic Protein 6HepcidinsIron

Identifiers

PMID37478395
PMCPMC10613724
OpenAlexW4384935467

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.