Evidence map›Paper›PMID 42509741›Full record

ReviewBiomolecules2026

Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.

Andrea Duminuco, Alessandro Costa, Federica Pilo, Salvatore Scarso, Cesarina Giallongo, Sebastiano Giallongo, Annalisa Santisi, Arianna Sbriglione, Laura Santocono, Giovanni Caocci and 1 more

Abstract readReview
In one paragraph

Review in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Andrea DuminucoDepartment of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.ORCID 0000-0002-9510-4755
Alessandro CostaHematology and BMT Unit, "A. Businco" Hospital, ARNAS Brotzu, 09121 Cagliari, Italy.ORCID 0000-0002-7726-2936
Federica PiloHematology and BMT Unit, "A. Businco" Hospital, ARNAS Brotzu, 09121 Cagliari, Italy.
Salvatore ScarsoDepartment of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, 37024 Verona, Italy.
Cesarina GiallongoDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Sebastiano GiallongoDepartment of Medicine and Surgery, University of Enna "Kore", 94100 Enna, Italy.
Annalisa SantisiHematology Unit with BMT, A.O.U. Policlinico "G.Rodolico-San Marco", 95123 Catania, Italy.
Arianna SbriglioneHematology Unit with BMT, A.O.U. Policlinico "G.Rodolico-San Marco", 95123 Catania, Italy.
Laura SantoconoHematology Unit with BMT, A.O.U. Policlinico "G.Rodolico-San Marco", 95123 Catania, Italy.
Giovanni CaocciHematology and BMT Unit, "A. Businco" Hospital, ARNAS Brotzu, 09121 Cagliari, Italy.
Giuseppe A PalumboDepartment of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.ORCID 0000-0003-1859-6319

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepcidin, a 25-amino-acid peptide hormone produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. By binding the cellular iron exporter ferroportin and inducing its internalization and lysosomal degradation, hepcidin restricts iron entry into plasma from enterocytes, macrophages, and hepatocytes. Its transcription is governed by an intricate molecular network that integrates iron status, erythropoietic demand, oxygen tension, and inflammation, with the BMP-HJV-ALK2/SMAD axis acting as the canonical activating pathway and erythroferrone (ERFE) and matriptase-2 (TMPRSS6) as physiological suppressors. Dysregulation of hepcidin underpins a wide spectrum of human diseases: insufficient hepcidin drives hereditary hemochromatosis and the iron overload of congenital and acquired ineffective erythropoiesis diseases and other ineffective erythropoiesis syndromes, whereas excessive or inappropriate hepcidin contributes to anemia of inflammation, anemia of chronic kidney disease, iron-restricted erythropoiesis in cancer, the iron-restrictive anemia of myelofibrosis, and pathogen-restrictive nutritional immunity. Within the myeloproliferative neoplasm spectrum, the divergent hepcidin patterns observed in polycythemia vera (suppressed) and myelofibrosis (inappropriately elevated through dual BMP/ACVR1/SMAD and IL-6/STAT3 hyperactivation) exemplify the clinical relevance of this axis and underpin two opposite pharmacologic strategies. Over the past decade, hepcidin pathway pharmacology has matured from proof-of-concept to regulatory milestones, shifting perspectives on several diseases and markedly improving clinical approaches.

Indexed as

Bone Morphogenetic ProteinsHepcidinsHomeostasisIronSmad ProteinsAnimalsHumansSignal TransductionBone Morphogenetic ProteinsHepcidinsIronSmad ProteinsACVR1/ALK2BMP–SMAD signalingchronic kidney diseasehepcidininflammationiron homeostasismyeloproliferative neoplasmsβ-thalassemia

Identifiers

PMID42509741
PMCPMC13407002

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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.