Involvement of Alpha-Klotho and Fibroblast Growth Factor Receptor in the Development of Secondary Hyperparathyroidism

• Published in: American journal of nephrology Vol. 31; no. 3; pp. 230 - 238
• Main Authors: Kumata, Chiaki, Mizobuchi, Masahide, Ogata, Hiroaki, Koiwa, Fumihiko, Nakazawa, Ai, Kondo, Fumiko, Kadokura, Yoshiyuki, Kinugasa, Eriko, Akizawa, Tadao
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2010
• Subjects: Adult; Aged; Cell Differentiation - physiology; Female; Glucuronidase - metabolism; Humans; Hyperparathyroidism, Secondary - metabolism; Hyperparathyroidism, Secondary - pathology; Immunohistochemistry; Ki-67 Antigen - metabolism; Male; Middle Aged; Original Report: Laboratory Investigation; Parathyroid Glands - metabolism; Parathyroid Glands - pathology; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Receptors, Calcium-Sensing - metabolism; α-Klotho; Fibroblast growth factor receptor; Secondary hyperparathyroidism
• ISSN: 0250-8095; 1421-9670
• DOI: 10.1159/000274483

Background/Aims: Fibroblast growth factor 23 (FGF23) has been shown to suppress parathyroid hormone (PTH) secretion. α-Klotho has been demonstrated to function as a fibroblast growth factor receptor (FGFR) cofactor for FGF23. Thus, both α-Klotho and FGFR may play roles in PTH synthesis and/or secretion. Functions of α-Klotho and FGFR in secondary hyperparathyroidism (SHPT) remain to be studied. The present studies explore the role of α-Klotho and FGFR in SHPT. Methods: Hyperplastic parathyroid glands (n = 44) were obtained from patients with SHPT. Results: Immunohistochemical study showed that both α-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 α-Klotho and FGFR1c (r 2 = 0.375, p < 0.01) indicating a cooperative system. Both α-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 α-Klotho correlated negatively with parathyroid cell proliferation, as confirmed by Ki67 staining (r 2 = 0.148, p < 0.05). Conclusion: Decreased expression of α-Klotho and FGFR1c in parallel with CaR expression and parathyroid cell growth may be involved in the pathogenesis of SHPT.