1 FGF23 - jaclap.org

1 Lab Clin Pract. 26(2) 111-116(2008) 111 23 (Ca) (fibroblast growth fac-tor: FGF)23 FGF23 FGF23 1 FGF23 FGF23 FGF 1) 3) FGF FGF(FGF1) FGF(FGF2) FGF FGF23 -trefoil 3 FGF FGF23 251 ( 1)1) 3) N 24 FGF23 227 FGF23 furin 179 Arg 180 Ser 4)

2 FGF23 N FGF C FGF23 FGF23 1 FGF23 FGF23 251 N 24 FGF23 furin 179 Arg(R) 180 Ser(S) FGF23 N FGF Lab Clin Pract. (2008) 112 2 1 N C 5) 22 FGF FGF23 FGF19 FGF21 FGF19 ( 2) 2a 2c - FGF23 FGF23 2a 2c - 6)

3 FGF23 1,25- D[1,25(OH)2D] 25- D[25(OH)D]-1 - 1,25(OH)2D 25(OH)D-24- 1,25(OH)2D 6) 1,25(OH)2D 3 FGF23 FGF23 2a 2c - (NaPi-2a, 2c) FGF23 1,25- D[1,25(OH)2D] 1,25(OH)2D FGF23 1,25(OH)2D ( 3) 2 FGF23 FGF23 (osteocyte) 7) FGF23 23 113 FGF23 FGF23 FGF23 FGF 4 FGF FGF (FGF receptor.

4 FGFR) FGF23 FGFR FGF23 FGF23 FGFR1c FGFR Klotho 8) Klotho Klotho 9) Klotho Klotho 1,25 (OH)2D FGF23 FGF23 Klotho 1,25(OH)2D 10) Klotho FGF23 8) Klotho FGF23 Klotho FGF23 FGF19 FGF19 FGF21 FGF19 FGF21 Klotho Klotho 11) FGF19 Klotho Klotho endocrine FGF hormone-like FGF 3 FGF23 ( 1)

5 FGF23 FGF23 I / 1 FGF23 FGF23 X / PHEX FGF23 / FGF23 FGF23 / DMP1 FGF23 / FGF23 McCune-Albright / GNAS1 FGF23 FGF23 GALNT3 FGF23 FGF23 FGF23 Klotho FGF23 PHEX: phosphate-regulating gene with homologies to endopeptidases on the X chromosome DMP1: dentin matrix protein 1 GNAS1: guanine nucleotide binding protein alpha stimulating activity polypeptide 1 GALNT3: UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 Lab Clin Pract.

6 (2008) 114 / / 3 X / (X-linked hypophosphatemic rickets/osteo-malacia: XLH) / (autosomal dominant hypophosphatemic rickets/osteomalacia: ADHR) / (autosomal recessive hypophosphatemic rickets/osteomalacia: ARHR) / (tumor-induced rickets/osteomalacia: TIO) McCune-Albright (fibrous dysplasia) 1,25(OH)2D 1,25(OH)2D 1,25(OH)2D D FGF23 XLH ARHR FGF23 12) 18) FGF23 FGF23 1,25(OH)2D (familial hyperphosphatemic tumoral cal-cinosis.

7 FHTC) FHTC FGF23 Klotho FHTC FGF23 GALNT3 Klotho 3 19) 21) FGF23 GALNT3 FGF23 FGF23 Klotho FGF23 FGF23 4 FGF23 FGF23 N C FGF23 13) FGF23 C 2 C 14) C FGF23 C FGF23 XLH TIO D Fa n co n i FGF23 FGF23 FGF23 22) TIO QOL TIO FGF23 TIO 20 23) FGF23 TIO TIO FGF23 TIO 23) 5 FGF23 FGF23 GALNT3 FHTC FGF23 23 115 FGF23 C FGF23 19)24) FGF23 FGF23 Klotho FHTC C FGF23 21)

8 FGF23 FGF23 25) FGF23 1 26) FGF23 FGF23 FGF23 6 FGF23 FGF23 FGF23 FGF23 FGF23 FGF23 FGF23 FGF23 1) Yamashita T, Yoshioka M, Itoh N. Identification of a novel fibroblast growth factor, FGF-23, preferen-tially expressed in the ventrolateral thalamic nu-cleus of the brain.

9 Biochem Biophys Res Commun 2000; 277: 494-8. 2) ADHR Consortium. Autosomal dominant hypo-phosphataemic rickets is associated with muta-tions in FGF23 . Nat Genet 2000; 26: 345-8. 3) Shimada T, Mizutani S, Muto T, et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A 2001; 98: 6500-5. 4) Benet-Pages A, Lorenz-Depiereux B, Zischka H, et al. FGF23 is processed by proprotein convertases but not by PHEX. Bone 2004; 35: 455-62. 5) Shimada T, Muto T, Urakawa I, et al. Mutant FGF-23 responsible for autosomal dominant hypophos-phatemic rickets is resistant to proteolytic cleav-age and causes hypophosphatemia in vivo.

10 Endo-crinology 2002; 143: 3179-82. 6) Shimada T, Hasegawa H, Yamazaki Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004; 19: 429-35. 7) Liu SG, Tang W, Zhou JP, et al. Distinct roles for intrinsic osteocyte abnormalities and systemic fac-tors in regulation of FGF23 and bone mineraliza-tion in Hyp mice. Am J Physiol Endocrinol Metab 2007; 293: E1636-44. 8) Urakawa I, Yamazaki Y, Shimada T, et al. Klotho converts canonical FGF receptor into a specific re-ceptor for FGF23 . Nature 2006; 444: 770-4. 9) Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome re-sembling ageing.