Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8
© 2017, The Japanese Society of Hematology. 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-thalass...
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th-cmuir.6653943832-402462017-09-28T04:08:30Z Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 Upanan S. McKie A. Latunde-Dada G. Roytrakul S. Uthaipibull C. Pothacharoen P. Kongtawelert P. Fucharoen S. Srichairatanakool S. © 2017, The Japanese Society of Hematology. 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. 2017-09-28T04:08:30Z 2017-09-28T04:08:30Z 2 Journal 09255710 2-s2.0-85017421334 10.1007/s12185-017-2231-3 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85017421334&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/40246 |
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© 2017, The Japanese Society of Hematology. 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. |
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Upanan S. McKie A. Latunde-Dada G. Roytrakul S. Uthaipibull C. Pothacharoen P. Kongtawelert P. Fucharoen S. Srichairatanakool S. |
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Upanan S. McKie A. Latunde-Dada G. Roytrakul S. Uthaipibull C. Pothacharoen P. Kongtawelert P. Fucharoen S. Srichairatanakool S. Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 |
author_facet |
Upanan S. McKie A. Latunde-Dada G. Roytrakul S. Uthaipibull C. Pothacharoen P. Kongtawelert P. Fucharoen S. Srichairatanakool S. |
author_sort |
Upanan S. |
title |
Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 |
title_short |
Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 |
title_full |
Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 |
title_fullStr |
Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 |
title_full_unstemmed |
Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 |
title_sort |
hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8 |
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2017 |
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85017421334&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/40246 |
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1681421774384791552 |