Fibroblast growth factor 23: fueling the fire
Mark Hanudel1, Harald Jüppner2, Isidro B Salusky1
1Division of Pediatric Nephrology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California, USA.
Kidney International
|October 16, 2016
Summary
Fibroblast growth factor 23 (FGF23) drives inflammation in chronic kidney disease by activating liver cells. Blocking this pathway with an antibody or cyclosporine reduces inflammatory markers like IL-6 and CRP.
Area of Science:
- Nephrology
- Immunology
- Endocrinology
Background:
- Systemic inflammation is prevalent in chronic kidney disease (CKD) and linked to increased mortality.
- Fibroblast growth factor 23 (FGF23) is implicated in CKD progression and associated complications.
Purpose of the Study:
- To investigate the role of FGF23 in mediating inflammation in CKD.
- To elucidate the molecular mechanisms by which FGF23 promotes hepatic inflammation.
Main Methods:
- The study examined the effect of FGF23 on hepatic cells.
- Investigated the involvement of fibroblast growth factor receptor 4 (FGFR4) and calcineurin/nuclear factor of activated T-cell (NFAT) signaling.
- Utilized an FGFR4 blocking antibody and cyclosporine for intervention.
Main Results:
- FGF23 significantly increased the hepatic expression and secretion of inflammatory cytokines, including interleukin-6 (IL-6) and C-reactive protein (CRP).
- FGF23 binds to hepatic FGFR4, activating the calcineurin/NFAT signaling pathway.
- Administration of an FGFR4 blocking antibody or cyclosporine effectively inhibited the proinflammatory effects of FGF23.
Conclusions:
- FGF23 contributes to uremic inflammation in CKD by activating hepatic FGFR4 and downstream signaling pathways.
- Targeting the FGF23-FGFR4 axis presents a potential therapeutic strategy for managing inflammation in CKD.
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