ライフサイエンスコーパス: FGF-23

1 haturic hormone fibroblast growth factor-23 (FGF-23).

2 pposite to those predicted by the actions of FGF-23.

3 nsport and restored the inhibitory effect of FGF-23.

4 stine with position 83 in FGF-8, FGF-19, and FGF-23.

5 ere completely extinguished by adjusting for FGF-23.

6 F was partially attenuated by adjustment for FGF-23.

7 lls are a Klotho-dependent target tissue for FGF-23.

8 atio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7).

9 Low concentrations of FGF-23 (10(-13) m) and PTH (10(-11) m) individually did

10 ansport, but the cells remained resistant to FGF-23 (10(-9) m).

11 e were resistant to the inhibitory effect of FGF-23 (10(-9) m).

12 -/- mice, resulting in prolonged survival of Fgf-23-/-/1alpha(OH)ase-/- double mutants.

13 le to increased urinary phosphate wasting in Fgf-23-/-/1alpha(OH)ase-/- mice, possibly as a consequen

14 oth the Fgf-23 and 1alpha-hydroxylase genes (Fgf-23-/-/1alpha(OH)ase-/-).

15 rtrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2).

16 ricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2).

17 ified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, w

18 at position 179 (R179Q), and synthetic human FGF-23(207-244)amide.

19 nst [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-lin

20 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or hig

21 FGF-23, a hormone involved in phosphorous and vitamin D

22 derived hormone fibroblast growth factor-23 (FGF-23) activates complexes composed of FGF receptors (F

23 Notably, recombinant FGF-23 administration similarly decreased the kidney exp

24 owest quartile, the two highest quartiles of FGF-23 also associated with a significantly elevated ris

25 -/- mice, we generated mice lacking both the Fgf-23 and 1alpha-hydroxylase genes (Fgf-23-/-/1alpha(OH

26 was a strong competitive interaction between FGF-23 and ADMA in the risk of renal events (P<0.01 in a

27 Both intact FGF-23 and ADMA predicted the incidence rate of renal ev

28 Increased FGF-23 and decreased 25(OH)D3 were independent predictor

29 with CKD had significantly higher levels of FGF-23 and fractional excretion of phosphorus; lower fra

30 new insights into the physiological roles of FGF-23 and Klotho.

31 inuric patients also displayed higher plasma FGF-23 and parathyroid hormone levels.

32 intermittent stimuli that lead to increased FGF-23 and PTH levels.

33 ated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increa

34 FGF-23 and PTH were inversely associated with estimated

35 FGF-23 and sFRP-4 inhibit 25-hydroxyvitamin D 1alpha-hyd

36 e for an in vivo inverse correlation between Fgf-23 and vitamin D activities and for the severe skele

37 Both fibroblast growth factor 23 (FGF-23) and asymmetric dimethylarginine (ADMA) are assoc

38 Fibroblast growth factor 23 (FGF-23) and Klotho are secretory proteins that regulate

39 eased levels of fibroblast growth factor-23 (FGF-23) and parathyroid hormone (PTH), but the stimuli f

40 factors such as fibroblast growth factor 23 (FGF-23) and PHEX are responsible for phosphate wasting.

41 ated with serum fibroblast growth factor-23 (FGF-23) and phosphorus levels that were 65 and 16% highe

42 m(2)), serum 25-hydroxyvitamin D (25(OH)D), FGF-23, and Klotho levels were measured at baseline and

43 fasting measurements of phosphorus, calcium, FGF-23, and PTH, but in this study, the hypothesis was t

44 Fgf-23-/- animals show extremely high serum levels of ph

45 ors can restore Klotho expression and unmask FGF-23 anticalcific effects.

46 Elevated levels of FGF-23 are associated with cardiovascular death and inci

47 ulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney dis

48 creatinine ratios were associated with high FGF-23 at baseline.

49 e NaPi-IIa expression secondary to decreased FGF-23 biologic activity.

50 lower urinary phosphate excretion and serum FGF-23 but not serum phosphate, klotho, vitamin D, or ca

51 enuated LVH in the Hyp mouse model of excess FGF-23, but did not induce a response in FGFR1(DT-cKO) m

52 Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic ricket

53 Median C-terminal FGF-23 (cFGF-23) levels were significantly higher in cas

54 To determine whether FGF-23 circulates in healthy persons and whether it is e

55 Here, we measured FGF-23 concentration in stored plasma samples from 1099

56 Higher circulating FGF-23 concentration is associated with incident AF and

57 osphorus concentration was 4.3 mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18

58 ing 7.5-year follow-up, each 20-pg/mL higher FGF-23 concentration was associated with a 19% greater r

59 portional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher ri

60 , and established cardiovascular biomarkers, FGF-23 concentration was independently associated with a

61 We tested the associations of circulating FGF-23 concentration with incident AF among 6398 partici

62 Plasma fibroblast growth factor 23 (FGF-23) concentration, plasma phosphate concentration, a

63 l study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricul

64 Higher serum FGF-23 concentrations are associated with subclinical ca

65 ney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality

66 Mean FGF-23 concentrations in the healthy adults and children

67 Circulating FGF-23 concentrations increase markedly in chronic kidne

68 FGF-23 concentrations were 481+/-528 RU per milliliter i

69 Although high FGF-23 concentrations were associated with each outcome

70 nalyses in the overall sample, increased log FGF-23 concentrations were independently associated with

71 duces elevation of both plasma phosphate and FGF-23 concentrations, potentially contributing to cardi

72 FGF-23 decreased significantly in the first month after

73 FGF-23 demonstrated an increased discriminatory power fo

74 levels in patients with CKD only; therefore, FGF-23 does not seem to be an acute postprandial regulat

75 Compared with the lowest quartile of FGF-23, each subsequent quartile associated with a progr

76 rmone (PTH) and fibroblast growth factor 23 (FGF-23) enhance phosphate excretion by the proximal tubu

77 Bone-derived FGF-23 (fibroblast growth factor-23) regulates phosphate

78 FGFR1 signaling (INFS) in the regulation of FGF-23 gene transcription in osteoblasts.

79 pathways are implicated in the regulation of FGF-23 gene transcription, but the molecular pathways re

80 Fibroblast growth factor 23 null mice (Fgf-23-/-) have a short lifespan and show numerous bioch

81 stablished cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical b

82 y, we have identified the cellular source of Fgf-23 in adult mice.

83 The role of FGF-23 in cardiovascular disease development in the gene

84 Our results indicate a novel role of Fgf-23 in developing premature aging-like features throu

85 Our studies suggest a novel role for FGF-23 in erythrocyte production and differentiation and

86 Genetic deletion of Fgf-23 in mice (Fgf-23(-/-)) results in hypervitaminosis

87 tion, we failed to detect the Phex substrate FGF-23 in osteoblasts.

88 ansplantation and to assess the influence of FGF-23 in the development of posttransplantation hypopho

89 Most importantly, administration of FGF-23 in wild-type mice results in a rapid decrease in

90 Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly

91 FGF-23 increases renal phosphorus excretion and inhibits

92 Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo

93 These studies indicate that FGF-23 inhibits phosphate transport in the mouse kidney

94 Fibroblast growth factor-23 (FGF-23) inhibits sodium-dependent phosphate transport in

95 parameters, including C-terminal fragment of FGF-23, intact parathyroid hormone, and 1,25(OH)(2)D(3),

96 Whether increased FGF-23 is a marker or a potential mechanism of myocardia

97 Future studies might investigate whether FGF-23 is a potential biomarker that can be used to guid

98 FGF-23 is an endocrine regulator of mineral metabolism a

99 Elevated FGF-23 is an independent risk factor for end-stage renal

100 vival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated co

101 FGF-23 is independently associated with an increased ris

102 Thus, higher FGF-23 is independently associated with greater risk of

103 FGF-23 is independently associated with left ventricular

104 However, whether FGF-23 is involved in the regulation of erythropoiesis i

105 FGF-23 is readily detectable in the plasma or serum of h

106 Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary

107 Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate exc

108 Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibi

109 Fibroblast growth factor-23 (FGF-23) is a phosphate regulatory hormone that directly

110 Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone.

111 Fibroblast growth factor 23 (FGF-23) is an endocrine regulator of phosphate and vitam

112 ulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with en

113 Fibroblast growth factor-23 (FGF-23) is one of the circulating phosphaturic factors a

114 evated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolis

115 S and vitamin D-fibroblast growth factor-23 (FGF-23)-Klotho pathways.

116 he signal transduction pathways initiated by FGF-23-Klotho prevent tissue atrophy by stimulating prol

117 h the risk of CKD progression is modified by FGF-23 level and provide further evidence that dysregula

118 metric dimethylarginine level and c-terminal FGF-23 level for the risk for renal events (P=0.001).

119 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR],

120 were confirmed in the MMKD cohort, in which FGF-23 level was again an effect modifier of the relatio

121 there are any differences in the changes in FGF-23 levels after surgery in KT recipients according t

122 ted with increased bone production and serum FGF-23 levels and decreased kidney membrane type IIa sod

123 ing hemodialysis treatment and then analyzed FGF-23 levels and mortality in a nested case-control sam

124 FGF-23 levels and the risk of developing posttransplanta

125 Increased FGF-23 levels appear to be independently associated with

126 In end-stage renal disease, high FGF-23 levels are associated with mortality.

127 Elevated FGF-23 levels are linked to CKD and greater risk of CVD,

128 In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently as

129 We hypothesized that increased FGF-23 levels at the initiation of hemodialysis would be

130 AC6 (AC6(-/-)) have increased plasma PTH and FGF-23 levels compared with wild-type (WT) mice but comp

131 nd differentiation and suggest that elevated FGF-23 levels contribute to the pathogenesis of anemia i

132 Compared with participants with FGF-23 levels in the lowest tertile, those in the highes

133 It is concluded that FGF-23 levels increase early in CKD before the developme

134 High FGF-23 levels promote left ventricular hypertrophy but n

135 lcium levels declined to normal by 10 weeks, FGF-23 levels remained elevated through 16 weeks, consis

136 FGF-23 levels rise in chronic kidney disease (CKD) despi

137 ble adjusted analyses showed that increasing FGF-23 levels were associated with a monotonically incre

138 FGF-23 levels were measured in 3,627 patients with SIHD

139 FGF-23 levels were measured in 980 patients with HF enro

140 Baseline and FGF-23 levels within the first posttransplantation month

141 rmore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced cardio

142 eased despite unchanged serum phosphorus and FGF-23 levels.

143 ADMA levels was highest in patients with low FGF-23 levels.

144 ), independent of eGFR; proteinuria, BP, and FGF-23 levels; and underlying renal diagnosis.

145 D3 (1,25D), and fibroblast growth factor 23 (FGF-23) maintains mineral homeostasis, in part by regula

146 FGF-23 may be a novel cardiovascular risk factor in the

147 Excessive FGF-23 may be involved in the hypophosphatemia and inapp

148 Increased FGF-23 may contribute to maintaining normal serum phosph

149 re are currently conflicting data on whether FGF-23 may exhibit direct vasculoprotective effects in C

150 FGF-23 may promote atrial fibrillation (AF) by inducing

151 FGF-23 measurements might improve the management of phos

152 FGF-23 mediated cellular activation of p-ERK, p-AKT, and

153 omalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosp

154 n homeostasis and impaired skeletogenesis in Fgf-23-/- mice are mediated through enhanced vitamin D a

155 re skeletal and soft tissue abnormalities of Fgf-23-/- mice being mediated through vitamin D.

156 Ablation of vitamin D from Fgf-23-/- mice resulted in further reduction of total bo

157 addition, loss of vitamin D activities from Fgf-23-/- mice reverses the severe hyperphosphatemia to

158 cations; ablation of vitamin D activity from Fgf-23-/- mice, by genetically deleting the 1alpha(OH)as

159 tly rescues premature aging-like features of Fgf-23-/- mice, resulting in prolonged survival of Fgf-2

160 sphate homeostasis and skeletogenesis in the Fgf-23-/- mice, we generated mice lacking both the Fgf-2

161 0 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6)

162 rences in changes in 25-(OH)-vitamin D, PTH, FGF-23, of F2-isoprostane levels between efavirenz and P

163 Finally, we show that the effect of FGF-23 on erythropoiesis is independent of the high vita

164 We aimed to assess the prognostic effect of FGF-23 on mortality in HF patients with a particular foc

165 dney disease, but the effect of the level of FGF-23 on mortality is unknown.

166 e greatly increased upon genetic ablation of Fgf-23 or Klotho, we find that these molecules have a du

167 Fgf-23(-/-) or Klotho(-/-) knockout mice exhibit several

168 sphate (filtered load), parathyroid hormone, FGF-23, or secreted frizzled related protein-4.

169 index (5% increase per 1-SD increase in log FGF-23; P=0.01) and risk of left ventricular hypertrophy

170 tricular mass index per 1-SD increase in log FGF-23; P=0.01; odds ratio of left ventricular hypertrop

171 In contrast, HMW-FGF-2 stimulated FGF-23 promoter activity in osteoblasts through a cAMP-d

172 the proximal FGF-23 promoter and stimulated FGF-23 promoter activity through PLCgamma/calcineurin/NF

173 cts of LMW-FGF-2 and HMW-FGF-23 to stimulate FGF-23 promoter activity.

174 ng to conserved cis-elements in the proximal FGF-23 promoter and stimulated FGF-23 promoter activity

175 contiguous with the NFAT binding site in the FGF-23 promoter.

176 FGF-23, PTH, 25(OH)D3, calcitriol, calcium, phosphate, a

177 In the CKD group (n = 1,128), the highest FGF-23 quartile had adjusted hazards ratios (HR) of 1.87

178 After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4-g g

179 on of FGF receptor substrate 2alpha, a major FGF-23 receptor substrate.

180 Here we report that loss of FGF-23 results in increased hematopoietic stem cell freq

181 Genetic deletion of Fgf-23 in mice (Fgf-23(-/-)) results in hypervitaminosis D, abnormal min

182 eptides such as fibroblast growth factor-23 (FGF-23), secreted frizzled related protein-4 (sFRP-4), m

183 man aortic smooth muscle cells responsive to FGF-23 signaling and unmasked potential anticalcific eff

184 second, as a cofactor required for vascular FGF-23 signaling.

185 In conclusion, in advanced CKD, FGF-23 strongly and independently associates with all-ca

186 In addition, FGF-23 synergizes with PTH to inhibit phosphate transpor

187 that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substitute

188 Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second

189 , inhibited the effects of LMW-FGF-2 and HMW-FGF-23 to stimulate FGF-23 promoter activity.

190 o integrate systemic and local regulation of FGF-23 transcription under diverse physiological and pat

191 We measured serum FGF-23 using the Kainos immunoassay.

192 ta support a new model of interactions among Fgf-23, vitamin D, and klotho, a gene described as being

193 FGF-23 was additionally measured in a second cohort comp

194 Elevated FGF-23 was associated more strongly with CHF than with a

195 Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of

196 scular risk factors, and medications, higher FGF-23 was independently associated with graded risk of

197 FGF-23 was independently associated with mortality with

198 Plasma FGF-23 was measured in 3,107 community-living persons >/

199 FGF-23 was not associated with carotid intima-media thic

200 A consistent change in FGF-23 was not identified.

201 Pretransplantation FGF-23 was the main predictor of posttransplantation pho

202 In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk

203 evels of the circulating phosphaturic factor FGF-23 were measured using a c-terminal assay both pre-

204 e, calcium, and fibroblast growth factor 23 (FGF-23) were up-regulated as early as week 4.

205 The association of FGF-23 with death, HF, and CVD in the general population

206 Associations of FGF-23 with each outcome were evaluated using Cox propor

207 We tested associations of FGF-23 with major subclinical and clinical cardiovascula