Molecular perspective of iron uptake, related diseases, and treatments

Negin Shokrgozar; Habib Allah Golafshan

doi:10.5045/br.2019.54.1.10

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Blood Res 2019; 54(1):

Published online March 31, 2019

https://doi.org/10.5045/br.2019.54.1.10

Molecular perspective of iron uptake, related diseases, and treatments

Negin Shokrgozar, and Habib Allah Golafshan^*

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Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Correspondence to : Correspondence to Habib Allah Golafshan, Ph.D. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Zand St., Shiraz, Iran. golafshansums@yahoo.com

Received: August 22, 2018; Revised: October 1, 2018; Accepted: October 1, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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.

Keywords Iron metabolism, Iron deficiency anemia, Iron regulation

Article

Review Article

Blood Res 2019; 54(1): 10-16

Published online March 31, 2019 https://doi.org/10.5045/br.2019.54.1.10

Molecular perspective of iron uptake, related diseases, and treatments

Negin Shokrgozar, and Habib Allah Golafshan^*

Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Correspondence to:Correspondence to Habib Allah Golafshan, Ph.D. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Zand St., Shiraz, Iran. golafshansums@yahoo.com

Received: August 22, 2018; Revised: October 1, 2018; Accepted: October 1, 2018

Abstract

Keywords: Iron metabolism, Iron deficiency anemia, Iron regulation

Abstract

Fig 1.

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Figure 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.

Blood Research 2019; 54: 10-16https://doi.org/10.5045/br.2019.54.1.10

Fig 2.

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Figure 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.

Blood Research 2019; 54: 10-16https://doi.org/10.5045/br.2019.54.1.10

Fig 3.

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Figure 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.

Blood Research 2019; 54: 10-16https://doi.org/10.5045/br.2019.54.1.10

Table 1 Diagnostic tests of iron deficiency anemia are observed in iron storage depletion, iron limitation for erythropoiesis, and progressive iron deficiency anemia. Note that microcytic-hypochromia is only observed in progressive iron deficiency.

Table 2 Causes of iron deficiency anemia.