Introduction: Body iron balance is maintained through the coordination between the so called "stores regulator" (i.e. iron accumulation), and "erythroid regulator" (as erythroid cells are the major iron consumers). Hepcidin, a liver-derived peptide that negatively regulates the iron exporter ferroportin to reduce iron absorption and mobilization is the downstream mediator of both regulators. Hepcidin synthesis, which is induced by iron and inflammation, is repressed in response to hypoxia, anemia and erythropoiesis, in order to increase iron availability. However, the signal(s) at the basis of this latter response are not fully understood. Materials and Methods: To elucidate the control of hepcidin expression by erythropoiesis, we investigated iron metabolism in wild type (Wt) animals and in transgenic mice chronically overexpressing erythropoietin and presenting a hematocrit —80% (Tg6). In addition, animals were treated with iron dextran (Wt_DXT and Tg6_DXT) and Tg6 mice were splenectomized to reduce erythropoiesis (Tg6_SPL). Results and Discussion: Hepcidin mRNA levels were strongly repressed in Tg6. Iron treatment increased hepcidin expression both in Wt_DXT and Tg6_DXT animals. Moreover, splenectomy enhanced hepcidin expression. Variations in hepcidin expression were accompanied by similar changes in the expression of BMP6, an iron-regulated inducer of hepcidin transcription, and the iron storage protein ferritin. Moreover, we found that the P-SMAD1/5/8 pathway, but not the MAPK/ERK pathway, were modulated in parallel to hepcidin. These results indicate that iron utilization by erythroid cells regulates hepcidin expression through an iron-dependent, BMP-mediated pathway. Conclusion: As opposed to conditions of expanded but ineffective erythropoiesis (e.g. (3-thalassemia), in which hepcidin expression is very low despite massive liver iron overload, our data suggest that in a situation of chronically elevated efficient erythropoiesis body iron overcomes the erythroid signal in hepcidin regulation.
Role of hepcidin in the interplay between body iron metabolism and erythropoiesis / E. Gammella, V. Diaz, S. Recalcati, P. Buratti, P. Santambrogio, V. Johannes, M. Gassmann, G. Cairo. ((Intervento presentato al convegno ICOC Paphos tenutosi a Cipro nel 2013.
|Titolo:||Role of hepcidin in the interplay between body iron metabolism and erythropoiesis|
GAMMELLA, ELENA (Primo)
CAIRO, GAETANO (Ultimo)
|Data di pubblicazione:||giu-2013|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Citazione:||Role of hepcidin in the interplay between body iron metabolism and erythropoiesis / E. Gammella, V. Diaz, S. Recalcati, P. Buratti, P. Santambrogio, V. Johannes, M. Gassmann, G. Cairo. ((Intervento presentato al convegno ICOC Paphos tenutosi a Cipro nel 2013.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|