title: Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8.
abstract: Atonal homolog 8 (ATOH8) is defined as a positive regulator of hepcidin transcription, which links erythropoietic activity with iron-sensing molecules. In the present study, we investigated the association between hepcidin and ATOH8 expression in β-thalassemia. We found that inhibition of hepcidin expression in β-thalassemia is correlated with reduced ATOH8 expression. Hepatic hepcidin 1 (Hamp1) and Atoh8 mRNA expression were down-regulated in β-thalassemic mice. Hepcidin (HAMP) and ATOH8 mRNA expression were consistently suppressed in Huh7 cells cultured in medium supplemented with β-thalassemia patient serum. The Huh7 cells, which were transfected with ATOH8-FLAG expression plasmid and cultured in the supplemented medium, exhibited increased levels of ATOH8 mRNA, ATOH8-FLAG protein, pSMAD1,5,8, and HAMP mRNA. Interestingly, over-expression of ATOH8 reversed the effects of hepcidin suppression induced by the β-thalassemia patient sera. In conclusion, hepcidin suppression in β-thalassemia is associated with the down-regulation of ATOH8 in response to anemia. We, therefore, suggest that ATOH8 is an important transcriptional regulator of hepcidin in β-thalassemia.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Supranee
authors.initials: S
authors.lastname: Upanan
authors.affiliation: Division of Diabetes and Nutritional Sciences, School of Medicine, King's College London, London, SE1 9NH, UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McKie
authors.affiliation: Division of Diabetes and Nutritional Sciences, School of Medicine, King's College London, London, SE1 9NH, UK.
authors.forename: Gladys O
authors.initials: GO
authors.lastname: Latunde-Dada
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani, 12120, Thailand.
authors.forename: Sittiruk
authors.initials: S
authors.lastname: Roytrakul
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani, 12120, Thailand.
authors.forename: Chairat
authors.initials: C
authors.lastname: Uthaipibull
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Peraphan
authors.initials: P
authors.lastname: Pothacharoen
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Prachya
authors.initials: P
authors.lastname: Kongtawelert
authors.affiliation: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakornpathom, 73170, Thailand.
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. ssrichai@med.cmu.ac.th.
authors.forename: Somdet
authors.initials: S
authors.lastname: Srichairatanakool
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D056726:Genetic Association Studies; D064451:Hepcidins / Q000235:genetics*; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D064451:Hepcidins; C449163:Atoh8 protein, mouse
keywords: ATOH8; Anemia; Hepcidin; Iron overload; β-Thalassemia