ライフサイエンスコーパス: FGF-23

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

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

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

4 ere completely extinguished by adjusting for FGF-23.

5 pposite to those predicted by the actions of 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 31 studies); 1.21 (95% CI, 1.15 to 1.28) for FGF-23 (30 studies); 2.07 (95% CI, 1.82 to 2.34) for TNF

21 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

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

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

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

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

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

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

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

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

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

31 In conclusion, FGF-23 and Klotho were associated with arterial calcific

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

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

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

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

36 FGF-23 and PTH were inversely associated with estimated

37 The association between FGF-23 and RV-dysfunction remained significant after the

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

39 tatistically significant association between FGF-23 and sodium avidity measured by fractional excreti

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

71 Circulating FGF-23 concentrations increase markedly in chronic kidne

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

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

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

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

76 FGF-23 decreased significantly in the first month after

77 FGF-23 demonstrated an increased discriminatory power fo

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

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

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

81 ase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix

82 Animal models implicate FGF-23 (fibroblast growth factor-23) as a direct contrib

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

84 FGF 23, FMD and hsCRP can stratify the risk of early CVD

85 zation, we found that NT-proBNP, BNP, TIMD4, FGF-23, GDF-15, PSP-D and SPON1, biomarkers broadly asso

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

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

88 ning 4 (TIMD4), fibroblast growth factor 23 (FGF-23), growth differentiation factor-15 (GDF-15), pulm

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

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

91 A-based confirmatory analysis of circulating FGF-23 in a large cohort of patients (n = 344, 72.7% NYH

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

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

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

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

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

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

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

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

100 e of klotho and fibroblast growth factor 23 (FGF-23) in human arterial remodeling across recent studi

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

102 FGF-23 increases renal phosphorus excretion and inhibits

103 Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo

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

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

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

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

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

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

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

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

112 Therefore, we aimed to evaluate whether FGF-23 is associated with parameters of cardiorenal dysf

113 FGF-23 is independently associated with an increased ris

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

115 FGF-23 is independently associated with left ventricular

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

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

118 Circulating FGF-23 is thus a biomarker of right ventricular dysfunct

119 our methods cannot rule out a small effect, FGF-23 is unlikely to be a primary driver of cardiorenal

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

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

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

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

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

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

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

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

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

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

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

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

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

133 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR],

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

135 egression analysis, revealed that the plasma FGF-23 level was most significantly associated with RV d

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

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

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

139 FGF-23 levels and the risk of developing posttransplanta

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

166 FGF-23 measurements might improve the management of phos

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

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

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

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

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

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

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

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

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

176 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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

198 Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were ass

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

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

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

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

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

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

205 , and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than

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

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

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

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

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

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

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

213 FGF-23 was associated with several metrics of disease se

214 FGF-23 was associated with the degree of RV dysfunction

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

216 FGF-23 was independently associated with mortality with

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

218 In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p =

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

220 FGF-23 was not associated with mortality in multivariabl

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

222 Likewise, FGF-23 was not independently associated with parameters

223 FGF-23 was not meaningfully associated with any cardiore

224 FGF-23 was positively correlated with arterial calcifica

225 ional hazard model revealed that circulating FGF-23 was significantly associated with adverse outcome

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

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

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

229 rmone (PTH) and fibroblast growth factor 23 (FGF-23) were studied up to 24-hours after Npt2a-I treatm

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

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

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

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