Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency
Abstract
Iron absorption is inadequately increased in patients with chronic haemolytic anaemia, which is commonly complicated by iron overload. Growth differentiation factor 15 (GDF15) has been identified as a bone marrow-derived factor that abrogates hepcidin-mediated protection from iron overload under conditions of increased erythropoiesis. Increased concentrations of GDF15 have been reported in beta-thalassaemia patients and GDF15 has been found to suppress hepcidin expression in vitro. To further study the interdependencies of iron metabolism and erythropoiesis in vivo, the concentrations of hepcidin and GDF15 were determined in sera from 22 patients with pyruvate kinase deficiency (PKD) and 21 healthy control subjects. In PKD patients, serum hepcidin levels were 13-fold lower than in controls (2.0 ng/ml vs. 26.2 ng/ml) and GDF15 was significantly higher (859 pg/ml vs. 528 pg/ml). Serum hepcidin concentrations correlated positively with haemoglobin and negatively with serum GDF15. These results suggest that GDF15 contributes to low hepcidin expression and iron loading in PKD.
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Increased GDF15 serum levels associate with syndromes of ineffective erythropoiesis, for example α- and β-thalassemia.
“While increased GDF15 serum levels associate with syndromes of ineffective erythropoiesis, for example α- and β-thalassemia”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [220]
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Regulation of erythropoiesis by hypoxia-inducible factors
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Self-citation
- Authors
- Finkenstedt, A., Bianchi, P., Theurl, I., Vogel, W., Witcher, D. R., Wroblewski, V. J., Murphy, A. T., Zanella, A., & Zoller, H.
- Affiliations
- Innsbruck Medical University (AT)
- University of Milan (IT)
- Eli Lilly (United States) (US)
- Corresponding author
- Zoller, Heinz
- ORCID
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2009-01-27
- Volume
- 144
- Issue
- 5
- Pages
- 789-793
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W1991054527
- Cited by
- 51
- References
- 23
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 6
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Universität Innsbruck
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- pyruvate kinase deficiency, GDF15, hepcidin, iron metabolism, iron overload, chronic hemolytic anemia, erythropoiesis, serum hepcidin levels, hemoglobin
- MeSH terms
- Adolescent, Adult, Aged, Erythropoiesis, Female, Hemoglobins, Humans, Iron, Male, Middle Aged, Pyruvate Kinase, Case-Control Studies, Reticulocyte Count, Statistics, Nonparametric, Iron Overload, Antimicrobial Cationic Peptides, Growth Differentiation Factor 15, Young Adult, Hepcidins
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