Ironing out Ferroportin

Drakesmith, Hal; Nemeth, Elizabeta; Ganz, Tomas

doi:10.1016/j.cmet.2015.09.006

Cited by 522 publications

(468 citation statements)

References 107 publications

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“…19,42 By contrast, in type 4B HH or atypical ferroportin disease due to mutations in SLC40A1 conferring partial or complete resistance to hepcidin, 67 serum hepcidin levels are substantially increased. 56 Some data support using hepcidin measurement as a guide for the follow-up genetic testing of IO patients, particularly in populations in whom classical type 1 HFErelated HH is rare.…”

Section: Diagnosis Of Io Disordersmentioning

confidence: 99%

Hepcidin in the diagnosis of iron disorders

Girelli

Nemeth

Swinkels

2016

Blood

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346

291

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The discovery of the iron-regulatory hormone hepcidin in 2001 has revolutionized our understanding of iron disorders, and its measurement should advance diagnosis/treatment of these conditions. Although several assays have been developed, a gold standard is still lacking, and efforts toward harmonization are ongoing. Nevertheless, promising applications can already be glimpsed, ranging from the use of hepcidin levels for diagnosing iron-refractory iron deficiency anemia to global health applications such as guiding safe iron supplementation in developing countries with high infection burden.

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Section: Diagnosis Of Io Disordersmentioning

confidence: 99%

Hepcidin in the diagnosis of iron disorders

Girelli

Nemeth

Swinkels

2016

Blood

Self Cite

346

291

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“…2). According to most recent basic studies [129,130], it is increasingly recognized that there are substantial quantitative differences between overall expression of ferroportin at intestinal level (normally dealing with low amount of iron, ~ 1-2 mg/die), as compared to the macrophage level (normally managing much more iron, ~ 20-25 mg/die). In other words, the amount of hepcidin needed for blocking iron absorption is likely much lower than that required for inhibiting ferroportin expressed by the innumerous iron recycling macrophages.…”

Section: Expanding Spectrum Of Clinical Use Of IV Ironmentioning

confidence: 99%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

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“…It is moderately expressed in hepatocytes, where the extent of its involvement in iron mobilisation from hepatic stores is unknown. 9 Despite references to FPN-independent mechanisms for hepatocyte iron export, there is at least enough evidence to implicate FPN in hepatic iron homeostasis, under certain conditions such as dietary iron deficiency. 10 Interestingly, functional genomic screening for cellular cofactors of HCV replication underscored the absence of hepcidin as deleterious for successful viral replication.…”

Section: Introductionmentioning

confidence: 99%

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

et al. 2016

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Mechanisms that favor Hepatitis C virus (HCV) persistence over clearance are unclear, but involve defective innate immunity. Chronic infection is characterized by hepatic iron overload, hyperferraemia and hyperferittinaemia. Hepcidin modulates iron egress via ferroportin and its storage in ferritin. Chronic HCV patients have decreased hepcidin, while HCV replication is modified by HAMP silencing. We aimed to investigate interactions between HCV and hepcidin, during acute and chronic disease, and putative alterations in cellular iron homeostasis that enhance HCV propagation and promote viral persistence. Thus, we used HCV JFH-1-infected co-cultures of Huh7.5 hepatoma and THP-1 macrophage cells, HCV patients' sera and Huh7 hepcidin-expressing cells transfected with HCV replicons. Hepcidin levels were elevated in acutely infected patients, but correlated with viral load in chronic patients. HAMP expression was up-regulated early in HCV infection in vitro, with corresponding changes in ferritin and FPN. Hepcidin overexpression enhanced both viral translation and replication. In HCV-infected co-cultures, we observed increased hepcidin, reduced hepatoma ferritin and a concurrent rise in macrophaghic ferritin over time. Altered iron levels complemented amplified replication in hepatoma cells and one replication round in macrophages. Iron-loading of macrophages led to enhancement of hepatic HCV replication through reversed ferritin "flow." Viral transmissibility from infected macrophages to na€ ıve hepatoma cells was induced by iron. We propose that HCV control over iron occurs both by intracellular iron sequestration, through hepcidin, and intercellular iron mobilisation via ferritin, as means toward enhanced replication. Persistence could be achieved through HCV-induced changes in macrophagic iron that enhances viral replication in these cells.

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Ironing out Ferroportin

Cited by 522 publications

References 107 publications

Hepcidin in the diagnosis of iron disorders

Hepcidin in the diagnosis of iron disorders

Modern iron replacement therapy: clinical and pathophysiological insights

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

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