Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBP alpha

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Jorge P Pinto (Author) Other; Sara Ribeiro (Author) Other; Helena Pontes (Author) Other; Shifaan Thowfeequ (Author) Other; David Tosh (Author) Other; Felix Carvalho (Author) FFUP; Graca Porto (Author) ICBAS

Journal

Title: Blood

Vol. 111

Pages: 5727-5733

ISSN: 0006-4971

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 180 Citations

Scopus - 204 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-003-YGP

DOI: 10.1182/blood-2007-08-106195

Abstract (EN): Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. Recent in vivo studies have shown that hepcidin is down-regulated by erythropoiesis, anemia, and hypoxia, which meets the need of iron input for erythrocyte production. Erythropoietin (EPO) is the primary signal that triggers erythropoiesis in anemic and hypoxic conditions. Therefore, a direct involvement of EPO in hepcidin regulation can be hypothesized. We report here the regulation of hepcidin expression by EPO, in a dose-dependent manner, in freshly isolated mouse hepatocytes and in the HepG2 human hepatocyte cell model. The effect is mediated through EPOR signaling, since hepcidin mRNA levels are restored by pretreatment with an EPOR-blocking antibody. The transcription factor C/EBP alpha showed a pattern of expression similar to hepcidin, at the mRNA and protein levels, following EPO and anti-EPOR treatments. Chromatin immunoprecipitation experiments showed a significant decrease of C/EBP alpha binding to the hepcidin promoter after EPO supplementation, suggesting the involvement of this transcription factor in the transcriptional response of hepcidin to EPO.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7