Hepcidin suppression in ß-thalassemia is associated with the down-regulation of atonal homolog 8.
Int J Hematol
; 106(2): 196-205, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28405918
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 ß-thalassemia. We found that inhibition of hepcidin expression in ß-thalassemia is correlated with reduced ATOH8 expression. Hepatic hepcidin 1 (Hamp1) and Atoh8 mRNA expression were down-regulated in ß-thalassemic mice. Hepcidin (HAMP) and ATOH8 mRNA expression were consistently suppressed in Huh7 cells cultured in medium supplemented with ß-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 ß-thalassemia patient sera. In conclusion, hepcidin suppression in ß-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 ß-thalassemia.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Down-Regulation
/
Gene Expression
/
Beta-Thalassemia
/
Basic Helix-Loop-Helix Transcription Factors
/
Genetic Association Studies
/
Hepcidins
Type of study:
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Int J Hematol
Year:
2017
Type:
Article
Affiliation country:
Thailand