Involvement of alpha-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism.
OBJECTIVE
Fibroblast growth factor 23 (FGF23) has been shown to suppress parathyroid hormone (PTH) secretion. alpha-Klotho has been demonstrated to function as a fibroblast growth factor receptor (FGFR) cofactor for FGF23. Thus, both alpha-Klotho and FGFR may play roles in PTH synthesis and/or secretion. Functions of alpha-Klotho and FGFR in secondary hyperparathyroidism (SHPT) remain to be studied. The present studies explore the role of alpha-Klotho and FGFR in SHPT.


METHODS
Hyperplastic parathyroid glands (n = 44) were obtained from patients with SHPT.


RESULTS
Immunohistochemical study showed that both alpha-Klotho and FGFR1c expression in hyperplastic glands was significantly decreased compared with that in normal glands (Klotho p < 0.01, and FGFR1c p < 0.05). A significant positive correlation was observed between alpha-Klotho and FGFR1c (r(2) = 0.375, p < 0.01) indicating a cooperative system. Both alpha-Klotho (r(2) = 0.235, p < 0.05) and FGFR1c (r(2) = 0.181, p < 0.05) correlated positively with the calcium-sensing receptor (CaR), which plays an important role in the development of SHPT. In addition, expression of alpha-Klotho correlated negatively with parathyroid cell proliferation, as confirmed by Ki67 staining (r(2) = 0.148, p < 0.05).


CONCLUSIONS
Decreased expression of alpha-Klotho and FGFR1c in parallel with CaR expression and parathyroid cell growth may be involved in the pathogenesis of SHPT.
Kumata
Chiaki
C
Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Mizobuchi
Masahide
M
Ogata
Hiroaki
H
Koiwa
Fumihiko
F
Nakazawa
Ai
A
Kondo
Fumiko
F
Kadokura
Yoshiyuki
Y
Kinugasa
Eriko
E
Akizawa
Tadao
T
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism
C000717427:FGF23 protein, human; D019394:Ki-67 Antigen; D044169:Receptors, Calcium-Sensing; D000089703:Fibroblast Growth Factor-23; D051496:Receptor, Fibroblast Growth Factor, Type 1; D005966:Glucuronidase; D000090265:Klotho Proteins