Hepcidin and its potential clinical utility

Abstract

A number of pathophysiological conditions are related to iron metabolism disturbances. Some of them are well known, others are newly discovered or special. Hepcidin is a newly identified iron metabolism regulating hormone, which could be a promising biomarker for many disorders. In this review, we provide background information about mammalian iron metabolism, cellular iron trafficking, and the regulation of expression of hepcidin. Beside these molecular biological processes, we summarize the methods that have been used to determine blood and urine hepcidin levels and present those pathological conditions (cancer, inflammation, neurological disorders) when hepcidin measurement may have clinical relevance.

Iron overload and altered iron metabolism in ovarian cancer

“…Ferroportin disease is characterized by mutations in FPN1 leading to hyperferritinemia and macrophage iron loading (Mayr et al, 2010) which may be due to altered trafficking of FPN1 to the cell surface (rate of synthesis, rate of internalization, and/or rate of degradation) (Ward and Kaplan, 2012). FPN1 levels can also be modulated via mechanisms distinct from HAMP such as post-transcriptionally by the IRP/IRE system (Ross et al, 2012; Miseta et al, 2015) as well as transcriptionally by (1) hypoxia, (2) transition metals and heme, as well as (3) inflammation (Ward and Kaplan, 2012). The presence of HAMP reduces circulating iron levels leading to intracellular sequestration of iron (Miseta et al, 2015).…”

“…FPN1 levels can also be modulated via mechanisms distinct from HAMP such as post-transcriptionally by the IRP/IRE system (Ross et al, 2012; Miseta et al, 2015) as well as transcriptionally by (1) hypoxia, (2) transition metals and heme, as well as (3) inflammation (Ward and Kaplan, 2012). The presence of HAMP reduces circulating iron levels leading to intracellular sequestration of iron (Miseta et al, 2015). HAMP/FPN1 axis is critical to body iron homeostasis; HAMP is upregulated by a variety of mechanisms involving transferrin receptor-2, hemochromatosis (HFE), bone morphogenic protein 6 (BMP6), and hemojuvelin (iron sensing extracellular system) (Miseta et al, 2015).…”

“…The presence of HAMP reduces circulating iron levels leading to intracellular sequestration of iron (Miseta et al, 2015). HAMP/FPN1 axis is critical to body iron homeostasis; HAMP is upregulated by a variety of mechanisms involving transferrin receptor-2, hemochromatosis (HFE), bone morphogenic protein 6 (BMP6), and hemojuvelin (iron sensing extracellular system) (Miseta et al, 2015). Erythropoietin negatively influences HAMP gene expression (Miseta et al, 2015).…”

“…HAMP/FPN1 axis is critical to body iron homeostasis; HAMP is upregulated by a variety of mechanisms involving transferrin receptor-2, hemochromatosis (HFE), bone morphogenic protein 6 (BMP6), and hemojuvelin (iron sensing extracellular system) (Miseta et al, 2015). Erythropoietin negatively influences HAMP gene expression (Miseta et al, 2015). Furthermore, IL-6 (which is upregulated in cancers and promotes cellular proliferation in human breast carcinoma (Sansone et al, 2007)) signals through the JAK/STAT signaling cascade and upregulates HAMP expression (Miseta et al, 2015).…”

“…Erythropoietin negatively influences HAMP gene expression (Miseta et al, 2015). Furthermore, IL-6 (which is upregulated in cancers and promotes cellular proliferation in human breast carcinoma (Sansone et al, 2007)) signals through the JAK/STAT signaling cascade and upregulates HAMP expression (Miseta et al, 2015). As indicated earlier, estrogen, vitamin D, and other hormones also influence HAMP expression (Miseta et al, 2015).…”