The DOI matches its Crossref record; 25 of the 26 references it cites were found in a registry or an index.
ER Stress Controls Iron Metabolism Through Induction of Hepcidin
Open accessAbstract
Hepcidin is a peptide hormone that is secreted by the liver and controls body iron homeostasis. Hepcidin overproduction causes anemia of inflammation, whereas its deficiency leads to hemochromatosis. Inflammation and iron are known extracellular stimuli for hepcidin expression. We found that endoplasmic reticulum (ER) stress also induces hepcidin expression and causes hypoferremia and spleen iron sequestration in mice. CREBH (cyclic AMP response element-binding protein H), an ER stress-activated transcription factor, binds to and transactivates the hepcidin promoter. Hepcidin induction in response to exogenously administered toxins or accumulation of unfolded protein in the ER is defective in CREBH knockout mice, indicating a role for CREBH in ER stress-regulated hepcidin expression. The regulation of hepcidin by ER stress links the intracellular response involved in protein quality control to innate immunity and iron homeostasis.
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“Cytokines such as interleukin (IL)-1, IL-6, or IL-22 as well as bacterial LPS or endoplasmic reticulum stress induce the formation of the master regulator of iron homeostasis, hepcidin, in the liver (Nemeth et al., 2003; Vecchi et al., 2009; Armitage et al., 2011).”
From Iron at the interface of immunity and infection (2014) · cites this paper as Vecchi et al., 2009
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“Endoplasmic reticulum (ER) stress is a pathological signal that modulates hepcidin synthesis, via cAMP response element-binding protein H (CREBH), an ER stress-activated transcription factor and the stress-inducible transcription factor and through CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) (173,…”
Background
Metadata
- Authors
- Vecchi, C., Montosi, G., Zhang, K., Lamberti, I., Duncan, S. A., Kaufman, R. J., & Pietrangelo, A.
- Affiliations
- Azienda Ospedaliero-Universitaria di Modena (IT)
- Wayne State University (US)
- Medical College of Wisconsin (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Pietrangelo, Antonello
- Venue
- Science
- Published
- 2009-08-14
- Volume
- 325
- Issue
- 5942
- Pages
- 877-880
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2923557
- OpenAlex
- W2017168923
- Cited by
- 310
- References
- 26
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 14 · 2022: 8 · 2021: 16 · 2020: 15 · 2019: 11 · 2018: 20 · 2017: 18 · 2016: 19 · 2015: 30 · 2014: 27 · 2013: 28 · 2012: 30
- FWCI
- 19.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (HL 52173, R01HL052173, P01HL057346)
- National Institute of Mental Health (R03MH089782)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK042394, DK42394, R37DK042394)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- endoplasmic reticulum stress, hepcidin, iron homeostasis, CREBH, unfolded protein response, protein quality control, innate immunity, hypoferremia, anemia of chronic disease, hemochromatosis, transcriptional regulation
- MeSH terms
- Animals, Endoplasmic Reticulum, Homeostasis, Humans, Immunity, Innate, Iron, Liver, Mutation, Promoter Regions, Genetic, Spleen, Stress, Physiological, Transcriptional Activation, 3T3 Cells, Cyclic AMP Response Element-Binding Protein, Protein Folding, Mice, Knockout, Antimicrobial Cationic Peptides, RNA Interference, Cell Line, Tumor, Mice, Hepcidins
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