Multiple faces of fibroblast growth factor-23

Area of Science:

• Endocrinology and Metabolism
• Cardiovascular Physiology
• Immunology

Background:

• Fibroblast growth factor-23 (FGF-23) is a hormone primarily produced by osteocytes in bone.
• FGF-23 plays a crucial role in mineral homeostasis, interacting with FGFR/α-Klotho complexes in the kidney.
• It forms a bone-kidney axis that regulates phosphate reabsorption, bone mineralization, and vitamin D metabolism.

Purpose of the Study:

• To review the multifaceted roles of FGF-23.
• To examine FGF-23's involvement in mineral metabolism, innate immunity, and cardiovascular outcomes.
• To elucidate the FGF-23 signaling pathways and their counter-regulatory effects against vitamin D.

Main Methods:

• Literature review of existing research on FGF-23.
• Analysis of FGF-23's interactions with FGFR/α-Klotho complexes.
• Examination of FGF-23's expression and function in various cell types, including macrophages.

Main Results:

• FGF-23 counter-regulates vitamin D's effects on innate immunity and cardiovascular function.
• Ectopic FGF-23 expression in macrophages creates a proinflammatory paracrine pathway.
• FGF-23 contributes to hypertension and left ventricular hypertrophy by affecting the renin-angiotensin system and sodium reabsorption.
• Potential FGF-23 effects on cardiac function and neutrophil responses independent of α-Klotho are debated and require further research.

Conclusions:

• FGF-23 is a key regulator in a bone-cardio-renal axis.
• It modulates mineral homeostasis, inflammation, and hemodynamics, often opposing vitamin D's actions.
• Further investigation is needed to fully understand FGF-23's independent effects and clinical implications.