@article{Rafiou Agoro_Min Young Park_Carole Le Henaff_Stanislovas Jankauskas_Alina Gaias_Gaozhi Chen_Moosa Mohammadi_Despina Sitara_2021, place={Pavia, Italy}, title={C-FGF23 peptide alleviates hypoferremia during acute inflammation}, volume={106}, url={https://haematologica.org/article/view/9694}, DOI={10.3324/haematol.2019.237040}, abstractNote={<p>Hypoferremia results as an acute phase response to infection and inflammation aiming to reduce iron availability to pathogens. Activation of toll-like receptors (TLRs), the key sensors of the innate immune system, induces hypoferremia mainly through the rise of the iron hormone hepcidin. Conversely, stimulation of erythropoiesis suppresses hepcidin expression via induction of the erythropoietin-responsive hormone erythroferrone. Iron deficiency stimulates transcription of the osteocyte-secreted protein FGF23. Here we hypothesized that induction of FGF23 in response to TLR4 activation is a potent contributor to hypoferremia and, thus, impairment of its activity may alleviate hypoferremia induced by lipopolysaccharide (LPS), a TLR 4 agonist. We used the C-terminal tail of FGF23 to impair endogenous full-length FGF23 signaling in wild-type mice, and investigated its impact on hypoferremia. Our data show that FGF23 is induced as early as pro-inflammatory cytokines in response to LPS, followed by upregulation of hepcidin and downregulation of erythropoietin (Epo) expression in addition to decreased serum iron and transferrin saturation. Further, LPS-induced hepatic and circulating hepcidin were significantly reduced by FGF23 signaling disruption. Accordingly, iron sequestration in liver and spleen caused by TLR4 activation was completely abrogated by FGF23 signaling inhibition, resulting in alleviation of serum iron and transferrin saturation deficit. Taken together, our studies highlight for the first time that inhibition of FGF23 signaling alleviates LPS-induced acute hypoferremia.</p&gt;}, number={2}, journal={Haematologica}, author={Rafiou Agoro and Min Young Park and Carole Le Henaff and Stanislovas Jankauskas and Alina Gaias and Gaozhi Chen and Moosa Mohammadi and Despina Sitara}, year={2021}, month={Feb.}, pages={391-403} }