Blood Res.  2019 Mar;54(1):10-16. 10.5045/br.2019.54.1.10.

Molecular perspective of iron uptake, related diseases, and treatments

• Shokrgozar N
• Golafshan

• KMID: 2451050
• DOI: http://doi.org/10.5045/br.2019.54.1.10

Abstract

Iron deficiency anemia and anemia of chronic disorders are the most common types of anemia. Disorders of iron metabolism lead to different clinical scenarios such as iron deficiency anemia, iron overload, iron overload with cataract and neurocognitive disorders. Regulation of iron in the body is a complex process and different regulatory proteins are involved in iron absorption and release from macrophages into hematopoietic tissues. Mutation in these regulatory genes is the most important cause of iron refractory iron deficiency anemia (IRIDA). This review provides a glance into the iron regulation process, diseases related to iron metabolism, and appropriate treatments at the molecular level.

Keyword

Iron metabolism; Iron deficiency anemia; Iron regulation

MeSH Terms

Absorption
Anemia
Anemia, Iron-Deficiency
Cataract
Genes, Regulator
Iron Overload
Iron*
Macrophages
Metabolism
Neurocognitive Disorders
Iron

Figure

• 

  Fig. 1 Erythroferrone is secreted from NRBCs in response to erythropoietin. ERFE causes increased iron absorption in the gastrointestinal system and release of iron from macrophages through ferroportin by decreasing hepcidin synthesis and provides sufficient iron for hematopoietic tissue (Kautz and Nemeth, 2014). Abbreviations: EPO, erythropoietin; HIF, hypoxia inducible factor; pO2, pressure of oxygen.

• 

  Fig. 2 Hepcidin mechanism. In inflammatory phenomena, increased hepcidin gene expression causes destruction of ferroportin. As a result, iron absorption and release of iron from macrophages is inhibited which eventually leads to anemia of chronic disorders. Abbreviations: BMP6, bone morphogenetic protein 6; BMPR, bone morphogenetic protein receptor; HFE, human hemochromatosis protein; HJV, hemojuvelin; IL-6, interleukin 6; IL-6R, interleukin 6 receptor; Tfr2, transferrin receptor 2.

• 

  Fig. 3 Systemic regulation of iron absorption through the gastrointestinal system and release of iron from macrophages. Abbreviations: DcytB, duodenal cytochrome B; Dmt1, divalent metal transporter 1; Fpn1, ferroportin1; GDF15, growth differentiation factor 15; Gpi-Cp, glycosylphosphatidylinositol-linked ceruloplasmin; HAMP, hepcidin anti-microbial peptide; HCP1, heme carrier protein 1; Heph, hephaestin; HO1, heme oxygenase 1; IL-R, interleukin receptor; MT2, matriptase 2; Mtf, metal regulatory transcription factor; PCBP1, poly (rC) binding protein 1; sCp, soluble ceruloplasmin; Tf, transferrin; TfR1, transferrin receptor 1; TWSG1, twisted gastrulation protein homolog 1.

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