BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism
Open accessAbstract
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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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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- 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)
- ORCID
- Yu, Binglan
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2014-09-25
- Volume
- 124
- Issue
- 13
- Pages
- 2116-2123
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4186540
- OpenAlex
- W2031409131
- Semantic Scholar
- d8b1ac4c36918f027439a986bdbec8a706763b90
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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