C-FGF23 peptide alleviates hypoferremia during acute inflammation
| Autor: | Alina Gaias, Carole Le Henaff, Min Young Park, Stanislovas Jankauskas, Rafiou Agoro, Despina Sitara, Gaozhi Chen, Moosa Mohammadi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Iron Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Hepcidins Hepcidin Internal medicine medicine Humans Inflammation medicine.diagnostic_test biology C-Peptide Transferrin saturation Chemistry Acute-phase protein Hematology Erythroferrone stomatognathic diseases 030104 developmental biology Endocrinology 030220 oncology & carcinogenesis Serum iron biology.protein TLR4 Erythropoiesis |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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