Dataset Information

Iron metabolism and iron disorders revisited in the hepcidin era.

ABSTRACT: Iron is biologically essential, but also potentially toxic; as such it is tightly controlled at cell and systemic levels to prevent both deficiency and overload. Iron regulatory proteins post-transcriptionally control genes encoding proteins that modulate iron uptake, recycling and storage and are themselves regulated by iron. The master regulator of systemic iron homeostasis is the liver peptide hepcidin, which controls serum iron through degradation of ferroportin in iron-absorptive enterocytes and iron-recycling macrophages. This review emphasizes the most recent findings in iron biology, deregulation of the hepcidin-ferroportin axis in iron disorders and how research results have an impact on clinical disorders. Insufficient hepcidin production is central to iron overload while hepcidin excess leads to iron restriction. Mutations of hemochro-matosis genes result in iron excess by downregulating the liver BMP-SMAD signaling pathway or by causing hepcidin-resistance. In iron-loading anemias, such as ?-thalassemia, enhanced albeit ineffective ery-thropoiesis releases erythroferrone, which sequesters BMP receptor ligands, thereby inhibiting hepcidin. In iron-refractory, iron-deficiency ane-mia mutations of the hepcidin inhibitor TMPRSS6 upregulate the BMP-SMAD pathway. Interleukin-6 in acute and chronic inflammation increases hepcidin levels, causing iron-restricted erythropoiesis and ane-mia of inflammation in the presence of iron-replete macrophages. Our improved understanding of iron homeostasis and its regulation is having an impact on the established schedules of oral iron treatment and the choice of oral versus intravenous iron in the management of iron deficiency. Moreover it is leading to the development of targeted therapies for iron overload and inflammation, mainly centered on the manipulation of the hepcidin-ferroportin axis.

SUBMITTER: Camaschella C

PROVIDER: S-EPMC7012465 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Iron metabolism and iron disorders revisited in the hepcidin era.

Camaschella Clara C Nai Antonella A Silvestri Laura L

Haematologica 20200131 2

Iron is biologically essential, but also potentially toxic; as such it is tightly controlled at cell and systemic levels to prevent both deficiency and overload. Iron regulatory proteins post-transcriptionally control genes encoding proteins that modulate iron uptake, recycling and storage and are themselves regulated by iron. The master regulator of systemic iron homeostasis is the liver peptide hepcidin, which controls serum iron through degradation of ferroportin in iron-absorptive enterocyte ...[more]

PMID: 31949017

Similar Datasets

Project description:BACKGROUND: Aim of this study was to evaluate whether the A736V TMPRSS6 polymorphism, a major genetic determinant of iron metabolism in healthy subjects, influences serum levels of hepcidin, the hormone regulating iron metabolism, and erythropoiesis in chronic hemodialysis (CHD). METHODS: To this end, we considered 199 CHD patients from Northern Italy (157 with hepcidin evaluation), and 188 healthy controls without iron deficiency, matched for age and gender. Genetic polymorphisms were evaluated by allele specific polymerase chain reaction assays, and hepcidin quantified by mass spectrometry. RESULTS: Serum hepcidin levels were not different between the whole CHD population and controls (median 7.1, interquartile range (IQR) 0.55-17.1 vs. 7.4, 4.5-17.9 nM, respectively), but were higher in the CHD subgroup after exclusion of subjects with relative iron deficiency (p?=?0.04). In CHD patients, the A736V TMPRSS6 polymorphism influenced serum hepcidin levels in individuals positive for mutations in the HFE gene of hereditary hemochromatosis (p?<?0.0001). In particular, the TMPRSS6 736 V variant was associated with higher hepcidin levels (p?=?0.017). At multivariate analysis, HFE and A736V TMPRSS6 genotypes predicted serum hepcidin independently of ferritin and C reactive protein (p?=?0.048). In patients without acute inflammation and overt iron deficiency (C reactive protein <1 mg/dl and ferritin >30 ng/ml; n?=?86), hepcidin was associated with lower mean corpuscular volume (p?=?0.002), suggesting that it contributed to iron-restricted erythropoiesis. In line with previous results, in patients without acute inflammation and severe iron deficiency the "high hepcidin" 736 V TMPRSS6 variant was associated with higher erythropoietin maintenance dose (p?=?0.016), independently of subclinical inflammation (p?=?0.02). CONCLUSIONS: The A736V TMPRSS6 genotype influences hepcidin levels, erythropoiesis, and anemia management in CHD patients. Evaluation of the effect of TMPRSS6 genotype on clinical outcomes in prospective studies in CHD may be useful to predict the outcomes of hepcidin manipulation, and to guide treatment personalization by optimizing anemia management.

Dataset Information

Iron metabolism and iron disorders revisited in the hepcidin era.

Publications

Iron metabolism and iron disorders revisited in the hepcidin era.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets