Browsing by Subject "FGF23"

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Expression of fibroblast growth factor 23 (FGF23) and αKlotho in two commercial laying hen strains fed with and without dietary mineral P supplements before and after the onset of the laying phase
(2025) Meier, Leonie; Wallauch, Nadine; Feger, Martina; Oster, Michael; Sommerfeld, Vera; Schmucker, Sonja; Wimmers, Klaus; Huber, Korinna; Stefanski, Volker; Rodehutscord, Markus; Föller, Michael
Maintenance of phosphate homeostasis is particularly critical in laying hens for bone formation and calcium mobilization. The supplementation of their feed with mineral phosphate is common although recent research questions the usual levels of supplementation. Phosphate homeostasis is classically regulated by active vitamin D (calcitriol) and parathyroid hormone, whereas fibroblast growth factor 23 (FGF23) and its co-receptor αKlotho are novel factors. FGF23 has emerged as an important disease biomarker and αKlotho as an anti-aging factor in mammals, however, little is known about their role in poultry. Here, we studied FGF23 and αKlotho expression in two commercial laying hen strains under conditions of dietary mineral phosphorus renunciation and sufficient phosphorus supply. Fifteen- and 20-week-old Lohmann Brown-Classic (LB) or LSL-Classic (LSL) hens were fed a standard maize-soybean-based diet containing 0 or 1 g/kg additional mineral phosphorus for 4 weeks. The animals were sacrificed, and gene expression studied in different organs by quantitative real-time PCR and protein expression by western blotting. Statistical correlation with further parameters of mineral metabolism was analyzed by Pearson’s correlation coefficient or Spearman’s Rho. As a result, FGF23 bone expression was significantly lower and hepatic FGF23 expression higher in 24-week-old than in 19-week-old hens. Bone, hepatic, and renal αKlotho expression was significantly higher in older than younger animals. Compared to LB hens, LSL hens exhibited higher hepatic αKlotho irrespective of diet and age. Dietary phosphorus content did not significantly affect FGF23 and αKlotho expression. Bone FGF23 expression was positively and hepatic FGF23 negatively associated with plasma phosphate concentration whereas bone FGF23 expression was negatively and hepatic FGF23 positively associated with plasma calcitriol concentration. To conclude, we uncovered a strong impact of age and strain on FGF23 and αKlotho expression in two high performance laying hen strains, effects possibly associated with initiation of the egg-laying phase. Moreover, the regulation of hepatic FGF23 expression differed from the regulation of bone FGF23 expression. Further studies are needed to elucidate the physiological relevance.
Prostaglandin E2 signaling through prostaglandin E receptor subtype 2 and Nurr1 induces fibroblast growth factor 23 production
(2024) Feger, Martina; Hammerschmidt, Katharina; Liesche, lona; Rausch, Steffen; Alber, Jana; Föller, Michael
Bone cells produce fibroblast growth factor 23 (FGF23), a hormone regulating renal phosphate and vitamin D homeostasis, and a paracrine factor produced in further tissues. Chronic kidney disease and cardiovascular disorders are associated with early elevations of plasma FGF23 levels associated with clinical outcomes. FGF23 production is dependent on many conditions including inflammation. Prostaglandin E2 (PGE2) is a major eicosanoid with a broad role in pain, inflammation, and fever. Moreover, it regulates renal blood flow, renin secretion, natriuresis as well as bone formation through prostaglandin E receptor 2 (EP2). Here, we studied the role of PGE2 and its signaling for the production of FGF23. Osteoblast-like UMR-106 cells were exposed to EP receptor agonists, antagonists or RNAi. Wild type and EP2 knockout mice were treated with stable EP2 agonist misoprostol. Fgf23 or Nurr1 gene expression was determined by quantitative real-time PCR, hormone and further blood parameters by enzyme-linked immunosorbent assay and colorimetric methods. PGE2 and EP2 agonists misoprostol and butaprost enhanced FGF23 production in UMR-106 cells, effects mediated by EP2 and transcription factor Nurr1. A single dose of misoprostol up-regulated bone Fgf23 expression and FGF23 serum levels in wild type mice with subtle effects on parameters of mineral metabolism only. Compared to wild type mice, the FGF23 effect of misoprostol was significantly lower in EP2-deficient mice. To conclude, PGE2 signaling through EP2 and Nurr1 induces FGF23 production. Given the broad physiological and pathophysiological implications of PGE2 signaling, this effect is likely of clinical relevance.
Short‐term fasting of mice elevates circulating fibroblast growth factor 23 (FGF23)
(2023) Feger, Martina; Alber, Jana; Strotmann, Jörg; Grund, Andrea; Leifheit‐Nestler, Maren; Haffner, Dieter; Föller, Michael
Aims: Phosphate and vitamin D homeostasis are controlled by fibroblast growth factor 23 (FGF23) from bone suppressing renal phosphate transport and enhancing 24-hydroxylase (Cyp24a1), thereby inactivating 1,25(OH)2D3. Serum FGF23 is correlated with outcomes in several diseases. Fasting stimulates the production of ketone bodies. We hypothesized that fasting can induce FGF23 synthesis through the production of ketone bodies. Methods: UMR106 cells and isolated neonatal rat ventricular myocytes (NRVM) were treated with ketone body β-hydroxybutyrate. Mice were fasted overnight, fed ad libitum, or treated with β-hydroxybutyrate. Proteins and further blood parameters were determined by enzyme-linked immunoassay (ELISA), western blotting, immunohistochemistry, fluorometric or colorimetric methods, and gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Results: β-Hydroxybutyrate stimulated FGF23 production in UMR106 cells in a nuclear factor kappa-light-chain enhancer of activated B-cells (NFκB)-dependent manner, and in NRVMs. Compared to fed animals, fasted mice exhibited higher β-hydroxybutyrate and FGF23 serum levels (based on assays either detecting C-terminal or intact, biologically active FGF23 only), cardiac, pancreatic, and thymic Fgf23 and renal Cyp24a1 expression, and lower 1,25(OH)2D3 serum concentration as well as renal Slc34a1 and αKlotho (Kl) expression. In contrast, Fgf23 expression in bone and serum phosphate, calcium, plasma parathyroid hormone (PTH) concentration, and renal Cyp27b1 expression were not significantly affected by fasting. Conclusion: Short-term fasting increased FGF23 production, as did administration of β-hydroxybutyrate, effects possibly of clinical relevance in view of the increasing use of FGF23 as a surrogate parameter in clinical monitoring of diseases. The fasting state of patients might therefore affect FGF23 tests.