The effect of erythropoietin on hepcidin expression in hepatic cells involves PI3K/mTOR signaling

MALTANERI ROMINA EUGENIA; SCHIAPPACASSE, AGUSTINA; CHAMORRO MARÍA EUGENIA; NESSE, ALCIRA; VITTORI DANIELA

Congreso; LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2018

Iron (Fe) homeostasis is essential for living organisms, since cells rely on this micronutrient for a variety of metabolic processes. This is particularly relevant for stress erythropoiesis, when Fe stored in hepatocytes must be mobilized for its uptake by bone marrow erythroblasts and the subsequent synthesis of hemoglobin. Hepatic stores are maintained by the peptide hepcidin (Hamp), which impairs Fe release by inducing degradation of the ferroportin transporter. In vivo, erythropoietin (Epo) has been shown to decrease Hamp levels, but questions arise about this being a direct effect on hepatocytes, and about the possible mechanisms involved.In order to study a possible direct action of Epo on Hamp production in hepatic cells, we assessed the ability of the cytokine to induce signaling in the human hepatoblastoma cell line HepG2. EpoR receptor expression was detected in this cell type (RT-PCR, flow cytometry). Epo (160 ng/mL) stimulated phosphorylation of the EpoR-associated kinase JAK2 (flow cytometry, Control: 20.9±3.1%, *Epo 5?: 38.4±5.2%, *P