Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8

Supranee Upanan; Andrew McKie; Gladys Latunde-Dada; Sittiruk Roytrakul; Chairat Uthaipibull; Peraphan Pothacharoen; Prachya Kongtawelert; Suthat Fucharoen; Somdet Srichairatanakool

doi:10.1007/s12185-017-2231-3

Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8

Supranee Upanan, Andrew McKie, Gladys Latunde-Dada, Sittiruk Roytrakul, Chairat Uthaipibull, Peraphan Pothacharoen, Prachya Kongtawelert, Suthat Fucharoen, Somdet Srichairatanakool^*

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	196–205
Number of pages	10
Journal	International Journal of Hematology
Early online date	12 Apr 2017
DOIs	https://doi.org/10.1007/s12185-017-2231-3
Publication status	Published - Aug 2017

Keywords

Anemia
ATOH8
Hepcidin
Iron overload
β-Thalassemia

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10.1007/s12185-017-2231-3

Hepcidin suppression in β-thalassemia_UPANAN_Accepted3April2017Publishedonline12April2017_GREEN AAMAccepted author manuscript, 670 KB

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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.",

keywords = "Anemia, ATOH8, Hepcidin, Iron overload, β-Thalassemia",

author = "Supranee Upanan and Andrew McKie and Gladys Latunde-Dada and Sittiruk Roytrakul and Chairat Uthaipibull and Peraphan Pothacharoen and Prachya Kongtawelert and Suthat Fucharoen and Somdet Srichairatanakool",

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T1 - Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8

AU - Upanan, Supranee

AU - McKie, Andrew

AU - Latunde-Dada, Gladys

AU - Roytrakul, Sittiruk

AU - Uthaipibull, Chairat

AU - Pothacharoen, Peraphan

AU - Kongtawelert, Prachya

AU - Fucharoen, Suthat

AU - Srichairatanakool, Somdet

PY - 2017/8

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N2 - 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.

AB - 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.

KW - Anemia

KW - ATOH8

KW - Hepcidin

KW - Iron overload

KW - β-Thalassemia

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SN - 0925-5710

SP - 196

EP - 205

JO - International Journal of Hematology

JF - International Journal of Hematology

ER -

Hepcidin suppression in β-thalassemia is associated with the down-regulation of atonal homolog 8

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