FGF23, Biomarker or Target?

Abstract

Fibroblast growth factor 23 (FGF23) plays a key role in the complex network between the bones and other organs. Initially, it was thought that FGF23 exclusively regulated phosphate and vitamin D metabolism; however, recent research has demonstrated that an excess of FGF23 has other effects that may be detrimental in some cases. The understanding of the signaling pathways through which FGF23 acts in different organs is crucial to develop strategies aiming to prevent the negative effects associated with high FGF23 levels. FGF23 has been described to have effects on the heart, promoting left ventricular hypertrophy (LVH); the liver, leading to production of inflammatory cytokines; the bones, inhibiting mineralization; and the bone marrow, by reducing the production of erythropoietin (EPO). The identification of FGF23 receptors will play a remarkable role in future research since its selective blockade might reduce the adverse effects of FGF23. Patients with chronic kidney disease (CKD) have very high levels of FGF23 and may be the population suffering from the most adverse FGF23-related effects. The general population, as well as kidney transplant recipients, may also be affected by high FGF23. Whether the association between FGF23 and clinical events is causal or casual remains controversial. The hypothesis that FGF23 could be considered a therapeutic target is gaining relevance and may become a promising field of investigation in the future.

Cardiac Remodeling in Chronic Kidney Disease

“…FGF23 signaling in the liver causes production of inflammatory cytokines. In the bone, FGF23 inhibits mineralization, leading to increased circulating phosphorus levels while reducing the production of erythropoietin (EPO) in the bone marrow [64]. All of the above-mentioned actions affect the outcome of CKD patients, and thus directly or indirectly lead to progression of cardiovascular disease.…”

“…Additionally, FGF23 signaling in the liver causes the production of inflammatory cytokines. In the bone, FGF23 inhibits mineralization, leading to increased circulating phosphorus levels and a reduction in the production of EPO [64,75]. Thus, the identification of FGF23 receptors in the respective organs will be crucial in future research since their selective blockade could be considered as a therapeutic target [64].…”

“…In the bone, FGF23 inhibits mineralization, leading to increased circulating phosphorus levels and a reduction in the production of EPO [64,75]. Thus, the identification of FGF23 receptors in the respective organs will be crucial in future research since their selective blockade could be considered as a therapeutic target [64]. On the other hand, FGF23 antibody treatment caused mineral disturbances, in particular hyperphosphatemia and was associated with increased mortality in a CKD rat model [105].…”

Protective Role of Vitamin D in Renal Tubulopathies

“…The overexpression of FGF23 is linked to hypophosphatemic rickets/osteomalacia, in contrast, a decrease in the action of FGF23 results in hyperphosphatemic calcinosis with high 1,25(OH)2D3 levels [90]. Vitamin D, through its action on VDR, regulates the promoter region in the FGF23 gene and locally produced 1,25(OH)2D3 in bone cells regulates FGF23 generation [91,92]. 25(OH)D3 hydroxylation is inhibited by FGF23 through the action of extracellular signal-regulated kinase 1/2 (ERK 1/2) [93].…”

Effect of Acute Physical Exercise with Moderate Intensities on FGF23 Gene Expression in Wistar Rat Heart

“…It was also mentioned that there was a possibility that the FGF23 in the heart is initially physiological and beneficial but after a certain time the concentrations could turn into unfavorable as seen,for example, in animal models with chronic kidney disease.The actual role of FGF23 in cardiovascular, whether only as a biomarker or as a target of therapy, is still unclear. 12 Therefore, this study explored the effect of acute physical exercise with moderate intensity for 3, 6, and 15 days on the expression of the FGF 23 gene in the heart of Wistar strain rats. This study used GAPDH as one of the most commonly used reference genes as an internal control, because its expression is very constant.…”