scholarly journals Dietary and Serum Phosphorus Regulate Fibroblast Growth Factor 23 Expression and 1,25-Dihydroxyvitamin D Metabolism in Mice

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5358-5364 ◽  
Author(s):  
Farzana Perwad ◽  
Nasreen Azam ◽  
Martin Y. H. Zhang ◽  
Takeyoshi Yamashita ◽  
Harriet S. Tenenhouse ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fold Increase ◽  
Mrna Abundance ◽  
Fibroblast Growth ◽  
Calvarial Bone ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D ◽  
Fgf 23

Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphorus (Pi) and vitamin D metabolism, but the mechanisms by which circulating FGF-23 itself is regulated are unknown. To determine whether the serum FGF-23 concentration is regulated by dietary intake of Pi, we fed wild-type (WT), Npt2a gene-ablated (Npt2a−/−), and Hyp mice diets containing varying Pi contents (0.02–1.65%). In WT mice, increases in dietary Pi intake from 0.02–1.65% induced a 7-fold increase in serum FGF-23 and a 3-fold increase in serum Pi concentrations. Across the range of dietary Pi, serum FGF-23 concentrations varied directly with serum Pi concentrations (r2 = 0.72; P < 0.001). In Npt2a−/− mice, serum FGF-23 concentrations were significantly lower than in WT mice, and these differences could be accounted for by the lower serum Pi levels in Npt2a−/− mice. The serum concentrations of FGF-23 in Hyp mice were 5- to 25-fold higher than values in WT mice, and the values varied with dietary Pi intake. Fgf-23 mRNA abundance in calvaria was significantly higher in Hyp mice than in WT mice on the 1% Pi diet; in both groups of mice, fgf-23 mRNA abundance in calvarial bone was suppressed by 85% on the low (0.02%) Pi diet. In WT mice fed the low (0.02%) Pi diet, renal mitochondrial 1α-hydroxylase activity and renal 1α-hydroxylase (P450c1α) mRNA abundance were significantly higher than in mice fed the higher Pi diets and varied inversely with serum FGF-23 concentrations (r2 = 0.86 and r2 = 0.64; P < 0.001, respectively). The present data demonstrate that dietary Pi regulates the serum FGF-23 concentration in mice, and such regulation is independent of phex function. The data suggest that genotype-dependent and dietary Pi-induced changes in the serum FGF-23 concentration reflect changes in fgf-23 gene expression in bone.

Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1α-hydroxylase expression in vitro

2007 ◽  
Vol 293 (5) ◽  
pp. F1577-F1583 ◽  
Author(s):  
Farzana Perwad ◽  
Martin Y. H. Zhang ◽  
Harriet S. Tenenhouse ◽  
Anthony A. Portale
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Signaling Pathway ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Vitamin D Metabolism ◽  
Fgf 23 ◽  
Dose Dependent

Fibroblast growth factor-23 (FGF-23) is critical to the pathogenesis of a distinct group of renal phosphate wasting disorders: tumor-induced osteomalacia, X-linked hypophosphatemia, and autosomal dominant and autosomal recessive hypophosphatemic rickets. Excess circulating FGF-23 is responsible for their major phenotypic features which include hypophosphatemia due to renal phosphate wasting and inappropriately low serum 1,25(OH)2D concentrations. To characterize the effects of FGF-23 on renal sodium-phosphate (Na/Pi) cotransport and vitamin D metabolism, we administered FGF-23(R176Q) to normal mice. A single injection (0.33 μg/g body wt) induced significant hypophosphatemia, 20 and 29% decreases ( P < 0.001) in brush-border membrane (BBM) Na/Pi cotransport at 5 and 17 h after injection, respectively, and comparable decreases in the abundance of type IIa Na/Pi cotransporter protein in BBM. Multiple injections (6, 12, and 24 μg/day for 4 days) induced dose-dependent decreases (38, 63, and 75%, respectively) in renal abundance of 1α-hydroxylase mRNA ( P < 0.05). To determine whether FGF-23(R176Q) exerts a direct action on 1α-hydroxylase gene expression, we examined its effects in cultured human (HKC-8) and mouse (MCT) renal proximal tubule cells. FGF-23(R176Q) (1 to 10 ng/ml) induced a dose-dependent decrease in 1α-hydroxylase mRNA with a maximum suppression of 37% ( P < 0.05). Suppression was detectable after 6 h of exposure and maximal after 21 h. In MCT cells, FGF-23(R176Q) suppressed 1α-hydroxylase mRNA and activated the ERK1/2 signaling pathway. The MAPK inhibitor PD98059 effectively abolished FGF-23-induced suppression of 1α-hydroxylase mRNA by blocking signal transduction via ERK1/2. These novel findings provide evidence that FGF-23 directly regulates renal 1α-hydroxylase gene expression via activation of the ERK1/2 signaling pathway.

scholarly journals PENGARUH PEMBERIAN 1,25 DIHYDROXYVITAMIN D (CALCITRIOL) TERHADAP KADAR FIBROBLAST GROWTH FACTOR-23 DAN ALBUMINURIA PADA PASIEN PENYAKIT GINJAL KRONIK STADIUM V YANG MENJALANI HEMODIALISIS

Biomedika ◽  
2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Intan Herlina ◽  
Bambang Purwanto ◽  
Sugiarto Sugiarto
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Drop Out ◽  
Fibroblast Growth ◽  
Angiotensin I ◽  
Chi Square ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Fgf 23

Penyebab utama morbiditas dan mortalitas pada pasien Penyakit Ginjal Kronik adalah insiden kardiovaskuler yang didasari oleh proses aterosklerosis yang menyebabkan meningkatnya morbiditas dan mortalitas. Ginjal merupakan tempat utama sintesa 1,25 Dihydroxyvitamin D (Calcitriol), sehingga dengan adanya kerusakan ginjal menyebabkan defisiensi 1,25 Dihydroxyvitamin D (Calcitriol). Pada pasien Penyakit Ginjal Kronik terjadi peningkatan Fibroblast Growth Factor-23 dan Albuminuria akibat dari aktifitas Renin Angiotensin Aldosteron Sistem. Aktifitas RAAS mempengaruhi 1,25 Dihydroxy vitamin D (Calcitriol), Fibroblast Growth Factor-23 melalui Angiotensin 2 dengan cara menghambat reseptor Angiotensin I (AT1) melalui Nicotinmide Adenine Dinucleotide Phosphate Oxidase (NADPH Oksidase) dan Stress Oxidativ. Beberapa penelitian menyimpulkan pemberian 1,25 Dihydroxyvitamin D (Calcitriol) mempunyai efek renoprotektif, anti inflamasi dan antiproteinuric dengan cara menghambat reseptor Angoitensin I (AT1) sehingga mengakibatkan menurunnya albuminuria. Tujuan Penelitian ini adalah untuk membuktikan pemberian 1,25 Dihydroxyvitamin D (Calcitriol) dapat menurunkan kadar Fibroblas Growth Factor-23 dan albuminuria pada pasien Penyakit Ginjal Kronik stadium V yang menjalani hemodialisis. Penelitian ini merupakan penelitian eksperimen dengan randomisasi, subyek penelitian 30 orang, dibagi dalam dua kelompok sampel, kelompok plasebo 15 orang dan kelompok perlakuan 15 orang. Dalam perjalanan, kelompok placebo drop out 4 pasien karena keluarga pasien tidak menyetujui untuk melanjutkan penelitian dan satu lagi mengalami perburukan, sehingga jumlah sampel menjadi 26 orang, terbagi menjadi kelompok placebo sebanyak 11 orang yang diberi placebo dan kelompok perlakuan 15 orang diberi calcitriol 1x0,5 μg peroral selama 4 minggu. Karakteristik penelitian yang berupa variabel kualitatif, uji homogenitas dilakukan menggunakan uji Chi Square. Uji beda dua Rerata menggunakan uji t pada p<0.005. Pada kelompok plasebo (n=11) ; Kadar Fibroblast Growth Factor-23 sebelum dan sesudah perlakuan (876,24±795,93 RU/mL vs 1235,69±791,71 RU/mL; p=0,059) dan Albuminuria (72,30±195,06 μg/ mg vs 320,14±208,90 μg/mg; p=0,001). Pada kelompok perlakuan (n=15); Kadar Fibroblast Growth Factor-23 sebelum dan sesudah perlakuan (1210,96±845,97 RU/mL vs 612,33±487,32 RU/mL; p=0,002) dan Albuminuria (206,63±327,25 μg/mg vs 192,89±316,00 μg/mg; p=0,001). Terdapat perbedaan yang bermakna pada selisih ratarata kadar Fibroblast Growth Factor-23 (Delta-FGF-23) sebelum dan sesudah perlakuan pada kelompok placebo vs kelompok perlakuan (-359,45±560,23 RU/mL vs 598,63±608,27 RU/mL; p=0,001) dan selisih rata-rata Albuminuria (Delta-albuminuria) sebelum dan sesudah perlakuan pada kelompok placebo vs kelompok perlakuan (-247,84±189,48 μg/mg vs 13,73±23,15μg/mg;p=0,001. Pemberian suplementasi 1,25 Dihydroxyvitamin D (calcitriol) menurunkan kadar FGF-23 albuminuria secara bermakna pada pasien penyakit ginjal kronik stadium V yang menjalani hemodialisisKata Kunci: Penyakit Ginjal Kronis Stadium V, 1,25 Dihydroxyvitamin D (Calcitriol), Fibroblast Growth Factor-23, Albuminuria

scholarly journals Increased Levels of sRAGE in Diabetic CKD-G5D Patients: A Potential Protective Mechanism against AGE-Related Upregulation of Fibroblast Growth Factor 23 and Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Dozio ◽  
Valentina Corradi ◽  
Elena Vianello ◽  
Elisa Scalzotto ◽  
Massimo de Cal ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cardiac Remodeling ◽  
Glycated Albumin ◽  
Fibroblast Growth Factor 23 ◽  
Protective Mechanism ◽  
Fibroblast Growth ◽  
Increased Risk ◽  
Fgf 23

Advanced glycation end products (AGEs) may induce cardiac remodeling in kidney disease by promoting fibroblast growth factor 23 (FGF-23) expression. Since AGEs are increased in diabetes mellitus (DM), our first aim was to evaluate the existence of any potential association between AGEs, FGF-23, inflammation, and increased cardiovascular risk in DM patients on dialysis (CKD-G5D). Secondarily, we explored the potential role of the soluble receptor for AGEs (sRAGE) as a marker of heart failure. Levels of glycated albumin (GA), sRAGE, c-terminal FGF-23 (cFGF-23), brain natriuretic peptide (BNP), and inflammatory mediators were compared between DM and non-DM CKD-G5D patients. The levels of sRAGE, cFGF-23, BNP, and proinflammatory markers were over the ranges of normality in both DM and non-DM groups. Only GA and sRAGE levels were increased in DM compared to non-DM patients. Plasma levels of sRAGE and CRP were the only independent predictors of BNP concentration. In conclusion, in DM CKD-G5D patients, sRAGE appeared to be a marker of cardiac remodeling. Indeed, its increase could be a potential protective mechanism against the increased risk of cardiovascular complications related to AGEs and inflammation. The causal relationship between sRAGE and cardiovascular risk in these patients needs to be further confirmed by mechanistic studies.

scholarly journals MP594THE RELATIONSHIP BETWEEN FIBROBLAST GROWTH FACTOR-23 (FGF-23) AND SELECTED CLINICAL AND LABORATORY PARAMETERS

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii648-iii649
Author(s):  
Danuta Fedak ◽  
Marek Kużniewski ◽  
Marcin Krzanowski ◽  
Paulina Dumnicka ◽  
Wladyslaw Sulowicz
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Laboratory Parameters ◽  
Fgf 23

Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men

2011 ◽  
Vol 26 (4) ◽  
pp. 857-864 ◽  
Author(s):  
Majd AI Mirza ◽  
Magnus K Karlsson ◽  
Dan Mellström ◽  
Eric Orwoll ◽  
Claes Ohlsson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fracture Risk ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Elderly Men ◽  
Fgf 23

scholarly journals Fibroblast Growth Factor 23-Producing Phosphaturic Mesenchymal Tumor with Extraordinary Morphology Causing Oncogenic Osteomalacia

Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 34
Author(s):  
Cornelia Then ◽  
Evelyn Asbach ◽  
Harald Bartsch ◽  
Niklas Thon ◽  
Christian Betz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Olfactory Neuroblastoma ◽  
Mesenchymal Tumor ◽  
Fibroblast Growth ◽  
Phosphaturic Mesenchymal Tumor ◽  
Oncogenic Osteomalacia ◽  
Pet Ct ◽  
Fgf 23

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.

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