Iron homeostasis is regulated by
hepcidin, a hepatic
hormone that controls
dietary iron absorption and plasma
iron concentration.
Hepcidin binds to the only known
iron export
protein,
ferroportin (FPN), which regulates its expression. The major factors that implicate
hepcidin regulation include
iron stores,
hypoxia,
inflammation, and erythropoiesis. When erythropoietic activity is suppressed,
hepcidin expression is hampered, leading to deficiency, thus causing an
iron overload in
iron-loading
anemia, such as β-
thalassemia.
Iron overload is the principal cause of mortality and morbidity in β-
thalassemia patients with or without
blood transfusion dependence. In the case of
thalassemia major, the primary cause of
iron overload is
blood transfusion. In contrast,
iron overload is attributed to
hepcidin deficiency and hyperabsorption of
dietary iron in non-transfusion
thalassemia.
Beta-thalassemia patients showed marked
hepcidin suppression,
anemia,
iron overload, and ineffective erythropoiesis (IE). Recent molecular research has prompted the discovery of new diagnostic markers and therapeutic targets for several diseases, including β-
thalassemia. In this review, signal transducers and activators of transcription (STAT) and SMAD (structurally similar to the small mothers against decapentaplegic in Drosophila) pathways and their effects on
hepcidin expression have been discussed as a therapeutic target for β-
thalassemia patients. Therefore, re-expression of
hepcidin could be a therapeutic target in the management of
thalassemia patients. Data from 65 relevant published experimental articles on
hepcidin and β-
thalassemia between January 2016 and May 2021 were retrieved by using PubMed and Google Scholar search engines. Published articles in any language other than English, review articles, books, or book chapters were excluded.