Fibroblast growth factor 23 is pumping iron: C-terminal-fibroblast growth factor 23 cleaved peptide and its function in iron metabolism

Guillaume Courbon; Valentin David

doi:10.1097/MNH.0000000000000995

Fibroblast growth factor 23 is pumping iron: C-terminal-fibroblast growth factor 23 cleaved peptide and its function in iron metabolism

Curr Opin Nephrol Hypertens. 2024 Apr 26. doi: 10.1097/MNH.0000000000000995. Online ahead of print.

Authors

Guillaume Courbon¹, Valentin David²

Affiliations

¹ INSERM U1059 SAINBIOSE, University of St Etienne, Mines St Etienne, St Etienne, France.
² Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

PMID: 38661434
DOI: 10.1097/MNH.0000000000000995

Abstract

Purpose of the review: Iron deficiency regulates the production of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) but also its cleavage, to generate both intact (iFGF23) and C-terminal (Cter)-FGF23 peptides. Novel studies demonstrate that independently of the phosphaturic effects of iFGF23, Cter-FGF23 peptides play an important role in the regulation of systemic iron homeostasis. This review describes the complex interplay between iron metabolism and FGF23 biology.

Recent findings: C-terminal (Cter) FGF23 peptides antagonize inflammation-induced hypoferremia to maintain a pool of bioavailable iron in the circulation. A key mechanism proposed is the down-regulation of the iron-regulating hormone hepcidin by Cter-FGF23.

Summary: In this manuscript, we discuss how FGF23 is produced and cleaved in response to iron deficiency, and the principal functions of cleaved C-terminal FGF23 peptides. We also review possible implications anemia of chronic kidney disease (CKD).