Cited by 74Iron Metabolism and DisordersTGF-β signaling in diseasesIron and Steelmaking Processes

BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism

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Mayeur, Claire, Leyton, Patricio A., Kolodziej, Starsha A., Yu, Binglan, Bloch, Kenneth D.·2014·Blood

Abstract

Expression of hepcidin, the hepatic hormone controlling iron homeostasis, is regulated by bone morphogenetic protein (BMP) signaling. We sought to identify which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is responsible for regulating hepcidin gene expression. We studied Bmpr2 heterozygous mice (Bmpr2(+/-)), mice with hepatocyte-specific deficiency of BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum hepcidin and iron levels, and tissue iron levels did not differ in wild-type mice, Bmpr2(+/-) mice, and mice in which either BMPR2 or ActR2a was deficient. Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene expression and serum hepcidin levels leading to severe iron overload. Iron injection increased hepatic hepcidin mRNA levels in mice deficient in either BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression. These results suggest that BMP type II receptors, BMPR2 and ActR2a, have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism.

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Crossref · 10.1182/blood-2014-04-572644

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  • BMP signaling is also necessary for hepcidin induction during inflammation.

    “Bone morphogenetic protein (BMP) signaling is also necessary for hepcidin induction during inflammation [18].”

    From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [18]

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  1. National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health UniGene. http://www.ncbi.nlm.nih.gov/unigene. Accessed April 22, 2014

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Authors
Mayeur, C., Leyton, P. A., Kolodziej, S. A., Yu, B., & Bloch, K. D.
Affiliations
  • Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, and
  • Harvard University (US)
Venue
Blood
Published
2014-09-25
Volume
124
Issue
13
Pages
2116-2123
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2031409131
Cited by
74
References
39
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 8 · 2017: 11 · 2016: 7 · 2015: 4 · 2014: 1
FWCI
5.44
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Fondation Leducq
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082971)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Physical Sciences › Engineering › Mechanical Engineering › Iron and Steelmaking Processes
Keywords
hepcidin, BMP type II receptor, BMPR2, BMP signaling, iron homeostasis, iron overload, hepatocytes, BMP6, receptor redundancy
MeSH terms
Animals, Female, Gene Expression Regulation, Heterozygote, Humans, Iron, Liver, Mutation, RNA, Messenger, Signal Transduction, Gene Deletion, Mice, Knockout, Iron Overload, Hepatocytes, Actin-Related Protein 2, Mice, Bone Morphogenetic Protein Receptors, Type II, Hepcidins

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