title: Iron dysregulation in beta-thalassemia.
abstract: Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide. Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron. The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis. Ferroportin is the sole cellular iron export protein, and its expression is regulated transcriptionally, post-transcriptionally and post-translationally. Hepcidin, a hormone produced by liver cells, post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes. Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in beta-thalassemia patients. Beta-thalassemia patients show marked hepcidin suppression, ineffective erythropoiesis, anemia and iron overload. Beta-thalassemia is common in the Mediterranean region, Southeast Asia and the Indian subcontinent, and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease. Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.
authors.affiliation: Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, 154 Rama 4 Road, Bangkok 10330, Thailand.
authors.forename: Kamonlak
authors.initials: K
authors.lastname: Leecharoenkiat
authors.affiliation: Department of Biology, Faculty of Science, Chiang Mai University, 239 Huaykaew Road, Amphur Muang, Chiang Mai 50200, Thailand.
authors.forename: Pathrapol
authors.initials: P
authors.lastname: Lithanatudom
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon 4 Road, Salaya, Nakhon Pathom 73170, Thailand.
authors.forename: Wannapa
authors.initials: W
authors.lastname: Sornjai
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon 4 Road, Salaya, Nakhon Pathom 73170, Thailand. Electronic address: duncan_r_smith@hotmail.com.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Smith
keywords: Beta-thalassemia; Ferroportin; Hepcidin; Iron overload