Inflammation regulates fibroblast growth factor 23 production

Abstract

Purpose of review Fibroblast growth factor 23 (FGF23) is a hormone secreted by osteocytes and osteoblasts that regulates phosphorus and vitamin D homeostasis. FGF23 levels increase progressively in chronic kidney disease (CKD), and FGF23 excess might be a causal factor of left ventricular hypertrophy, CKD progression and death. Therefore, understanding the molecular mechanisms that control FGF23 production is a critical to design therapies to lower FGF23 levels. The present review focuses on the role of inflammatory stimuli on FGF23 regulation and summarizes recent studies that support a novel framework linking inflammation to FGF23 regulation. Recent findings Inflammation and iron deficiency, which are common occurrences in CKD have emerged as novel FGF23 regulators. Recent findings show that inflammation increases FGF23 production in bone through direct and iron-related indirect mechanisms. In these settings, Hypoxia Inducible Factor (HIF)-1α orchestrates FGF23 transcription in response to inflammation and is primarily responsible for coordinating FGF23 production and cleavage. Summary We demonstrate that inflammation increases FGF23 production and may contribute to elevated FGF23 levels in CKD. Osseous HIF-1α may represent a therapeutic target to lower FGF23 levels in CKD patients and minimize the negative consequences associated with FGF23 excess.

Strength of Fibroblast Growth Factor 23 as a Cardiovascular Risk Predictor in Chronic Kidney Disease Weaken by ProBNP Adjustment

“…Next, our analyses focused upon the interactions of heart failure and iron deficiency with plasma FGF23, while several other non-CKD-MBD regulators of FGF23 have been suggested, including the presence of inflammatory diseases [42]. However, at least within CARE FOR HOMe, adjustment for inflammatory markers did not modify our study results.…”

HIF‐prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism

“…The study suggested that HIF‐PHIs might enhance phosphate‐induced vascular smooth muscle cell calcification in CKD or ESRD patients with poorly controlled mineral bone metabolism . A molecular link also exists between HIF and FGF23 signaling, which may negatively impact cardiovascular risk in HIF‐PHI‐treated CKD patients . Another potential adverse effect that may be observed in CKD patients on HIF‐PHI therapy is hepatic toxicity.…”

Advanced glycation end products stimulate gene expression of fibroblast growth factor 23

“…NFκB is the pivotal transcription factor in inflammatory processes . Previous studies have already established a clear role for inflammation in the synthesis of FGF23 . In detail, inflammatory cytokines have been shown to induce FGF23 production , and some acute and chronic inflammatory diseases are associated with an elevated serum FGF23 level .…”