MECHANISM OF ACTION OF ERYTHROPOIETIN ON HEPCIDIN REGULATION IN MACROPHAGES

IOLSTER JOAQUÍN; VITTORI, DANIELA; NESSE, ALCIRA; VILLAROSA, JULIETA; CHAMORRO MARÍA EUGENIA

Mar del Plata

Congreso; LXVII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2022

SAIC-SAI-FAIC-SAFIS

Iron (Fe) homeostasis, required for essential cellular processes, is systemically regulated by hepcidin (Hep). Fe deficiency, stress erythropoiesis or erythropoietin (Epo) administration inhibit Hep expression, increasing systemic Fe availability. We have recently described a direct effect of Epo and that of the erythropoietic intermediary erythroferrone (ERFE) on Hep regulation in hepatocytes. Since this Epo action has not been evaluated in macrophages fundamental cells in Fe homeostasis the aim of this work was to investigate mechanisms by which Epo regulates Hep in these cells.We previously observed the presence of the Epo receptor (EpoR) and a inhibitory effect of Epo (160 ng/mL, 6 h) on Hep mRNA levels in the THP-1 monocytic cell line differentiated to macrophages with PMA. To determine if this action occurs through the homodimeric receptor, EpoR was silenced using a specific siRNA, which prevented the suppressive effect of Epo on Hep expression (RT-PCR, a.u.: Control=0.46±0.05; *Epo=0.19±0.03; siEpoR+Epo=0.53±0.04; *siGFP+Epo=0.21±0.05, *P